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Clinical Trial Results:
Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Other Pediatric Vaccines in Healthy Toddlers

Summary
EudraCT number	2018-001472-38
Trial protocol	Outside EU/EEA
Global end of trial date	19 Jul 2018

Results information
Results version number	v1
This version publication date	08 Aug 2019
First version publication date	08 Aug 2019
Other versions	v2

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

MET57

ISRCTN number

US NCT number

NCT03205371

WHO universal trial number (UTN)

U1111-1161-2787

Sponsor organisation name

Sanofi Pasteur

Sponsor organisation address

Discovery Drive, Swiftwater, PA, United States, 18370-0187

Public contact

Trial Transparency Team, Sanofi Pasteur, Contact-US@sanofi.com

Scientific contact

Trial Transparency Team, Sanofi Pasteur, Contact-US@sanofi.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-001930-PIP01-16

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

27 Feb 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

19 Jul 2018

Was the trial ended prematurely?

Main objective of the trial

To describe the immunogenicity profile of MenACYW conjugate vaccine administered alone or concomitantly with licensed pediatric vaccine(s) ((measles-mumps-rubella vaccine [MMR] +Varicella, diphtheria, tetanus, acellular pertussis, hepatitis B, poliomyelitis, and Haemophilus influenzae type-b Conjugate vaccine [DTaP-IPV-HB-Hib], or pneumococcal Conjugate vaccine [PCV13]).

Protection of trial subjects

Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment were also available on site in case of any immediate allergic reactions.

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Nov 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Mexico: 400

Country: Number of subjects enrolled

Russian Federation: 400

Country: Number of subjects enrolled

Korea, Republic of: 213

Country: Number of subjects enrolled

Thailand: 170

Worldwide total number of subjects

1183

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

1183

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Study subjects were enrolled in South Korea, Mexico, the Russian Federation, and Thailand from 07 November 2016 to 13 June 2018.

Screening details

A total of 1183 subjects were enrolled and randomized in the study.

Period 1 title

Overall study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

South Korea(Group1): MenACYW Conjugate +MMR+ Varicella Vaccine

Arm description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of Meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine, measles-mumps-rubella vaccine (MMR) vaccine, and varicella vaccine on Day 0.

Arm type

Experimental

Investigational medicinal product name

MenACYW Conjugate vaccine: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 milliliter (mL), intramuscular, single dose on Day 0.

Investigational medicinal product name

Measles, Mumps, and Rubella Vaccine

Investigational medicinal product code

Other name

M-M-R® II

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

0.5 mL, subcutaneous, single dose on Day 0.

Investigational medicinal product name

Varicella Vaccine

Investigational medicinal product code

Other name

VARIVAX

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

0.5 mL, subcutaneous, single dose on Day 0.

South Korea (Group 2): MenACYW Conjugate Vaccine

Arm description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Arm type

Experimental

Investigational medicinal product name

MenACYW Conjugate vaccine: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular, single dose on Day 0.

South Korea (Group 3): MMR + Varicella Vaccine

Arm description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MMR vaccine and varicella vaccine on Day 0.

Arm type

Active comparator

Investigational medicinal product name

Measles, Mumps, and Rubella Vaccine

Investigational medicinal product code

Other name

M-M-R® II

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

0.5 mL, subcutaneous, single dose on Day 0.

Investigational medicinal product name

Varicella Vaccine

Investigational medicinal product code

Other name

VARIVAX

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

0.5 mL, subcutaneous, single dose on Day 0.

Thailand (Group 10): MenACYW Conjugate +MMR+Varicella Vaccine

Arm description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine , MMR vaccine, and Varicella vaccine on Day 0.

Arm type

Experimental

Investigational medicinal product name

MenACYW Conjugate vaccine: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular, single dose on Day 0.

Investigational medicinal product name

Measles, Mumps, and Rubella Vaccine

Investigational medicinal product code

Other name

M-M-R® II

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

0.5 mL, subcutaneous, single dose on Day 0.

Investigational medicinal product name

Varicella Vaccine

Investigational medicinal product code

Other name

VARIVAX

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

0.5 mL, subcutaneous, single dose on Day 0.

Thailand (Group 11): MenACYW Conjugate Vaccine

Arm description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Arm type

Experimental

Investigational medicinal product name

MenACYW Conjugate vaccine: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular, single dose on Day 0.

Thailand (Group 12): MMR + Varicella Vaccine

Arm description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MMR vaccine and varicella vaccine on Day 0.

Arm type

Experimental

Investigational medicinal product name

Measles, Mumps, and Rubella Vaccine

Investigational medicinal product code

Other name

M-M-R® II

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

0.5 mL, subcutaneous, single dose on Day 0.

Investigational medicinal product name

Varicella Vaccine

Investigational medicinal product code

Other name

VARIVAX

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

0.5 mL, subcutaneous, single dose on Day 0.

Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine

Arm description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine and diphtheria, tetanus, acellular pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type-b (DTaP-IPV-HB-Hib) vaccine on Day 0.

Arm type

Experimental

Investigational medicinal product name

MenACYW Conjugate vaccine: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular, single dose on Day 0.

Investigational medicinal product name

DTaP-IPV-HB-Hib: Diphtheria, tetanus, pertussis (acellular), hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b conjugate vaccine

Investigational medicinal product code

Other name

Hexaxim ®

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular, single dose on Day 0.

Mexico (Group 5): MenACYW Conjugate Vaccine

Arm description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Arm type

Experimental

Investigational medicinal product name

MenACYW Conjugate vaccine: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular, single dose on Day 0.

Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine

Arm description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of DTaP-IPV-HB-Hib Vaccine on Day 0.

Arm type

Active comparator

Investigational medicinal product name

DTaP-IPV-HB-Hib: Diphtheria, tetanus, acellular pertussis, hepatitis B, poliomyelitis, and Haemophilus influenzae type-b conjugate vaccine

Investigational medicinal product code

Other name

Hexaxim ®

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular, single dose on Day 0.

Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine

Arm description

Healthy, meningococcal-vaccine naïve toddlers (aged 15 to 23 months) received single dose of MenACYW Conjugate and pneumococcal Conjugate vaccine (PCV13) on Day 0.

Arm type

Experimental

Investigational medicinal product name

MenACYW Conjugate vaccine: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular, single dose on Day 0.

Investigational medicinal product name

PCV13: Pneumococcal 13-valent Conjugate Vaccine

Investigational medicinal product code

Other name

Prevenar 13

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular, single dose on Day 0.

Russian Federation (Group 8): MenACYW Conjugate Vaccine

Arm description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 14 months or 16 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Arm type

Experimental

Investigational medicinal product name

MenACYW Conjugate vaccine: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular, single dose on Day 0.

Russian Federation (Group 9): PCV13 Vaccine

Arm description

Healthy, meningococcal-vaccine naïve toddlers (aged 15 to 23 months) received single dose of PCV13 vaccine on Day 0.

Arm type

Active comparator

Investigational medicinal product name

PCV13: Pneumococcal 13-valent Conjugate Vaccine

Investigational medicinal product code

Other name

Prevenar 13

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular, single dose on Day 0.

Number of subjects in period 1	South Korea(Group1): MenACYW Conjugate +MMR+ Varicella Vaccine	South Korea (Group 2): MenACYW Conjugate Vaccine	South Korea (Group 3): MMR + Varicella Vaccine	Thailand (Group 10): MenACYW Conjugate +MMR+Varicella Vaccine	Thailand (Group 11): MenACYW Conjugate Vaccine	Thailand (Group 12): MMR + Varicella Vaccine	Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine	Mexico (Group 5): MenACYW Conjugate Vaccine	Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine	Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine	Russian Federation (Group 8): MenACYW Conjugate Vaccine	Russian Federation (Group 9): PCV13 Vaccine
Started	107	53	53	86	42	42	200	100	100	200	100	100
Safety Analysis Set	103	52	53	86	42	42	200	100	100	200	100	99
Per-protocol Analysis Set	92 ^[1]	45 ^[2]	50 ^[3]	85 ^[4]	42	42	155 ^[5]	79 ^[6]	68 ^[7]	196 ^[8]	96 ^[9]	92 ^[10]
Completed	103	52	53	86	42	42	190	97	95	200	100	99
Not completed	4	1	0	0	0	0	10	3	5	0	0	1
Consent withdrawn by subject	4	1	-	-	-	-	4	-	2	-	-	1
Adverse event, non-fatal	-	-	-	-	-	-	-	1	-	-	-	-
Lost to follow-up	-	-	-	-	-	-	5	2	3	-	-	-
Protocol deviation	-	-	-	-	-	-	1	-	-	-	-	-

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Per-Protocol analysis set included all subjects who received at least 1 dose of study vaccine, and had no protocol deviations.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Per-Protocol analysis set included all subjects who received at least 1 dose of study vaccine, and had no protocol deviations.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Per-Protocol analysis set included all subjects who received at least 1 dose of study vaccine, and had no protocol deviations.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Per-Protocol analysis set included all subjects who received at least 1 dose of study vaccine, and had no protocol deviations.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Per-Protocol analysis set included all subjects who received at least 1 dose of study vaccine, and had no protocol deviations.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Per-Protocol analysis set included all subjects who received at least 1 dose of study vaccine, and had no protocol deviations.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Per-Protocol analysis set included all subjects who received at least 1 dose of study vaccine, and had no protocol deviations.
[8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Per-Protocol analysis set included all subjects who received at least 1 dose of study vaccine, and had no protocol deviations.
[9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Per-Protocol analysis set included all subjects who received at least 1 dose of study vaccine, and had no protocol deviations.
[10] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Per-Protocol analysis set included all subjects who received at least 1 dose of study vaccine, and had no protocol deviations.

Baseline characteristics

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Reporting group title

South Korea(Group1): MenACYW Conjugate +MMR+ Varicella Vaccine

Reporting group description

Reporting group title

South Korea (Group 2): MenACYW Conjugate Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Reporting group title

South Korea (Group 3): MMR + Varicella Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MMR vaccine and varicella vaccine on Day 0.

Reporting group title

Thailand (Group 10): MenACYW Conjugate +MMR+Varicella Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine , MMR vaccine, and Varicella vaccine on Day 0.

Reporting group title

Thailand (Group 11): MenACYW Conjugate Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Reporting group title

Thailand (Group 12): MMR + Varicella Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MMR vaccine and varicella vaccine on Day 0.

Reporting group title

Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine

Reporting group description

Reporting group title

Mexico (Group 5): MenACYW Conjugate Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Reporting group title

Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of DTaP-IPV-HB-Hib Vaccine on Day 0.

Reporting group title

Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 15 to 23 months) received single dose of MenACYW Conjugate and pneumococcal Conjugate vaccine (PCV13) on Day 0.

Reporting group title

Russian Federation (Group 8): MenACYW Conjugate Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 14 months or 16 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Reporting group title

Russian Federation (Group 9): PCV13 Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 15 to 23 months) received single dose of PCV13 vaccine on Day 0.

Reporting group values	South Korea(Group1): MenACYW Conjugate +MMR+ Varicella Vaccine	South Korea (Group 2): MenACYW Conjugate Vaccine	South Korea (Group 3): MMR + Varicella Vaccine	Thailand (Group 10): MenACYW Conjugate +MMR+Varicella Vaccine	Thailand (Group 11): MenACYW Conjugate Vaccine	Thailand (Group 12): MMR + Varicella Vaccine	Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine	Mexico (Group 5): MenACYW Conjugate Vaccine	Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine	Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine	Russian Federation (Group 8): MenACYW Conjugate Vaccine	Russian Federation (Group 9): PCV13 Vaccine	Total
Number of subjects	107	53	53	86	42	42	200	100	100	200	100	100	1183
Age categorical
Units: Subjects
Age continuous
Units: months
arithmetic mean (standard deviation)	12.7 ( 1.58 )	12.7 ( 1.50 )	12.3 ( 0.96 )	12.4 ( 0.90 )	12.4 ( 0.88 )	12.8 ( 1.76 )	16.4 ( 2.73 )	16.8 ( 2.83 )	16.8 ( 2.99 )	16.5 ( 2.36 )	16.0 ( 3.10 )	16.3 ( 2.26 )	-
Gender categorical
Units: Subjects
Female	49	18	29	47	23	23	93	46	48	78	51	45	550
Male	58	35	24	39	19	19	107	54	52	122	49	55	633
Race
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0
Asian	1	0	0	86	42	42	0	0	1	2	1	4	179
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0	0	0	0	0	0	0	0
White	0	0	0	0	0	0	200	100	99	198	99	96	792
More than one race	0	0	0	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	106	53	53	0	0	0	0	0	0	0	0	0	212
Ethnicity
Units: Subjects
Hispanic or Latino	0	0	0	0	0	0	200	100	98	4	0	1	403
Not Hispanic or Latino	0	0	0	86	42	42	0	0	2	196	100	99	567
Unknown or Not Reported	107	53	53	0	0	0	0	0	0	0	0	0	213

End points

Top of page

Reporting group title

South Korea(Group1): MenACYW Conjugate +MMR+ Varicella Vaccine

Reporting group description

Reporting group title

South Korea (Group 2): MenACYW Conjugate Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Reporting group title

South Korea (Group 3): MMR + Varicella Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MMR vaccine and varicella vaccine on Day 0.

Reporting group title

Thailand (Group 10): MenACYW Conjugate +MMR+Varicella Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine , MMR vaccine, and Varicella vaccine on Day 0.

Reporting group title

Thailand (Group 11): MenACYW Conjugate Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Reporting group title

Thailand (Group 12): MMR + Varicella Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MMR vaccine and varicella vaccine on Day 0.

Reporting group title

Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine

Reporting group description

Reporting group title

Mexico (Group 5): MenACYW Conjugate Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Reporting group title

Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of DTaP-IPV-HB-Hib Vaccine on Day 0.

Reporting group title

Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 15 to 23 months) received single dose of MenACYW Conjugate and pneumococcal Conjugate vaccine (PCV13) on Day 0.

Reporting group title

Russian Federation (Group 8): MenACYW Conjugate Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 14 months or 16 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Reporting group title

Russian Federation (Group 9): PCV13 Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 15 to 23 months) received single dose of PCV13 vaccine on Day 0.

Subject analysis set title

Groups 1 and10:MenACYW Conjugate Vaccine+MMR+Varicella Vaccine

Subject analysis set type

Per protocol

Subject analysis set description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) from South Korea and Thailand received single dose of MenACYW Conjugate vaccine, MMR vaccine, and varicella vaccine on Day 0.

Subject analysis set title

Groups 2 and 11: MenACYW Conjugate Vaccine

Subject analysis set type

Per protocol

Subject analysis set description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) from South Korea and Thailand received single dose of MenACYW conjugate vaccine on Day 0.

Subject analysis set title

Groups 3 and 12: MMR + Varicella Vaccine

Subject analysis set type

Per protocol

Subject analysis set description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) from South Korea and Thailand received single dose of MMR vaccine and varicella vaccine on Day 0.

Primary: Geometric Mean Titers of MenACYW Antibodies Following Injection With MenACYW Conjugate Vaccine Administered Alone or Concomitantly With Other Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11

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End point title

Geometric Mean Titers of MenACYW Antibodies Following Injection With MenACYW Conjugate Vaccine Administered Alone or Concomitantly With Other Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11 ^[1] ^[2]

End point description

Antibody titers of MenACYW were measured by serum bactericidal assay using human complement (hSBA) assay. Data for this endpoint was reported for the combined population of Groups 1 and 10, Groups 2 and 11. Analysis was performed on PPAS which included subjects who received at least one dose of the study vaccine(s), had a valid post-vaccination blood sample result and no protocol deviations. Data for this endpoint were not planned to be collected and analysed for Groups 3, 6, 9, and 12.

End point type

Primary

End point timeframe

Day 0 and Day 30 post-vaccination

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was evaluated for reported arms only.

End point values	Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine	Mexico (Group 5): MenACYW Conjugate Vaccine	Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine	Russian Federation (Group 8): MenACYW Conjugate Vaccine	Groups 1 and10:MenACYW Conjugate Vaccine+MMR+Varicella Vaccine	Groups 2 and 11: MenACYW Conjugate Vaccine
Number of subjects analysed	155	79	196	96	177	87
Units: titers (1/dilution)
geometric mean (confidence interval 95%)
Serogroup A: Day 0	5.35 (4.82 to 5.94)	5.49 (4.66 to 6.45)	5.99 (5.30 to 6.76)	8.54 (6.47 to 11.3)	5.20 (4.56 to 5.93)	6.10 (5.00 to 7.44)
Serogroup A: Day 30	31.4 (25.9 to 38.1)	37.8 (28.5 to 50.2)	24.6 (20.2 to 30.1)	49.0 (36.8 to 65.3)	43.9 (37.4 to 51.6)	30.0 (23.1 to 39.0)
Serogroup C: Day 0	2.21 (2.11 to 2.31)	2.16 (2.00 to 2.34)	2.77 (2.43 to 3.16)	3.69 (2.84 to 4.81)	2.37 (2.11 to 2.65)	2.58 (2.15 to 3.10)
Serogroup C: Day 30	749 (633 to 886)	666 (538 to 825)	205 (156 to 269)	309 (218 to 437)	876 (725 to 1057)	600 (456 to 790)
Serogroup Y: Day 0	2.63 (2.37 to 2.92)	2.94 (2.45 to 3.53)	2.90 (2.56 to 3.28)	3.49 (2.68 to 4.53)	3.14 (2.78 to 3.54)	3.12 (2.58 to 3.78)
Serogroup Y: Day 30	79.7 (65.7 to 96.6)	90.9 (66.8 to 124)	139 (111 to 173)	172 (130 to 229)	88.9 (75.1 to 105)	60.0 (47.3 to 76.3)
Serogroup W: Day 0	2.41 (2.22 to 2.62)	2.16 (2.04 to 2.30)	2.93 (2.54 to 3.38)	3.62 (2.73 to 4.79)	2.15 (2.00 to 2.30)	2.31 (2.02 to 2.64)
Serogroup W: Day 30	40.0 (32.5 to 49.3)	50.9 (37.2 to 69.8)	57.4 (47.9 to 68.6)	57.0 (44.3 to 73.5)	46.8 (39.1 to 56.0)	35.5 (27.6 to 45.7)

No statistical analyses for this end point

Primary: Percentage of Subjects With Antibody Titers >=1:4 and 1:8 Against Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or With Other Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11

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End point title

Percentage of Subjects With Antibody Titers >=1:4 and 1:8 Against Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or With Other Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11 ^[3] ^[4]

End point description

Antibody titers of Men A, C, Y, and W were measured by hSBA assay. Data for this endpoint was reported for the combined population of Groups 1 and 10, Groups 2 and 11. Analysis was performed on PPAS. Data for this endpoint were not planned to be collected and analysed for Groups 3, 6, 9, and 12.

End point type

Primary

End point timeframe

Day 0 and Day 30 post-vaccination

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was evaluated for reported arms only.

End point values	Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine	Mexico (Group 5): MenACYW Conjugate Vaccine	Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine	Russian Federation (Group 8): MenACYW Conjugate Vaccine	Groups 1 and10:MenACYW Conjugate Vaccine+MMR+Varicella Vaccine	Groups 2 and 11: MenACYW Conjugate Vaccine
Number of subjects analysed	155	79	196	96	177	87
Units: percentage of subjects
number (confidence interval 95%)
Serogroup A: Day 0 (>=1:4)	82.6 (75.7 to 88.2)	82.3 (72.1 to 90.0)	82.1 (76.1 to 87.2)	85.4 (76.7 to 91.8)	75.1 (68.1 to 81.3)	82.8 (73.2 to 90.0)
Serogroup A: Day 0 (>=1:8)	45.8 (37.8 to 54.0)	46.8 (35.5 to 58.4)	49.0 (41.8 to 56.2)	54.2 (43.7 to 64.4)	37.9 (30.7 to 45.4)	44.8 (34.1 to 55.9)
Serogroup A: Day 30 (>=1:4)	98.1 (94.4 to 99.6)	97.5 (91.2 to 99.7)	94.9 (90.8 to 97.5)	97.9 (92.7 to 99.7)	98.9 (96.0 to 99.9)	95.4 (88.6 to 98.7)
Serogroup A: Day 30 (>=1:8)	92.9 (87.7 to 96.4)	89.9 (81.0 to 95.5)	83.7 (77.7 to 88.6)	90.6 (82.9 to 95.6)	97.7 (94.3 to 99.4)	92.0 (84.1 to 96.7)
Serogroup C: Day 0 (>=1:4)	12.3 (7.5 to 18.5)	7.6 (2.8 to 15.8)	19.9 (14.5 to 26.2)	36.5 (26.9 to 46.9)	9.6 (5.7 to 14.9)	16.1 (9.1 to 25.5)
Serogroup C: Day 0 (>=1:8)	1.9 (0.4 to 5.6)	1.3 (0.0 to 6.9)	8.7 (5.1 to 13.5)	17.7 (10.7 to 26.8)	4.0 (1.6 to 8.0)	6.9 (2.6 to 14.4)
Serogroup C: Day 30 (>=1:4)	100.0 (97.6 to 100.0)	100.0 (95.4 to 100.0)	98.5 (95.6 to 99.7)	99.0 (94.3 to 100.0)	100.0 (97.9 to 100.0)	100.0 (95.8 to 100.0)
Serogroup C: Day 30 (>=1:8)	100.0 (97.6 to 100.0)	100.0 (95.4 to 100.0)	93.9 (89.5 to 96.8)	99.0 (94.3 to 100.0)	100.0 (97.9 to 100.0)	100.0 (95.8 to 100.0)
Serogroup Y: Day 0 (>=1:4)	19.4 (13.5 to 26.5)	25.3 (16.2 to 36.4)	21.9 (16.4 to 28.4)	32.3 (23.1 to 42.6)	32.2 (25.4 to 39.6)	28.7 (19.5 to 39.4)
Serogroup Y: Day 0 (>=1:8)	11.0 (6.5 to 17.0)	12.7 (6.2 to 22.0)	14.3 (9.7 to 20.0)	15.6 (9.0 to 24.5)	18.6 (13.2 to 25.2)	17.2 (10.0 to 26.8)
Serogroup Y: Day 30 (>=1:4)	98.7 (95.4 to 99.8)	100.0 (95.4 to 100.0)	98.5 (95.6 to 99.7)	99.0 (94.3 to 100.0)	99.4 (96.9 to 100.0)	96.6 (90.3 to 99.3)
Serogroup Y: Day 30 (>=1:8)	98.7 (95.4 to 99.8)	98.7 (93.1 to 100.0)	97.4 (94.1 to 99.2)	97.9 (92.7 to 99.7)	99.4 (96.9 to 100.0)	95.4 (88.6 to 98.7)
Serogroup W: Day 0 (>=1:4)	14.8 (9.6 to 21.4)	8.9 (3.6 to 17.4)	16.8 (11.9 to 22.8)	26.0 (17.6 to 36.0)	5.1 (2.4 to 9.4)	11.5 (5.7 to 20.1)
Serogroup W: Day 0 (>=1:8)	7.7 (4.1 to 13.1)	2.5 (0.3 to 8.8)	12.8 (8.4 to 18.3)	20.8 (13.2 to 30.3)	1.1 (0.1 to 4.0)	2.3 (0.3 to 8.1)
Serogroup W: Day 30 (>=1:4)	97.4 (93.5 to 99.3)	96.2 (89.3 to 99.2)	95.9 (92.1 to 98.2)	96.9 (91.1 to 99.4)	98.9 (96.0 to 99.9)	96.6 (90.3 to 99.3)
Serogroup W: Day 30 (>=1:8)	90.3 (84.5 to 94.5)	92.4 (84.2 to 97.2)	94.4 (90.2 to 97.2)	95.8 (89.7 to 98.9)	96.0 (92.0 to 98.4)	92.0 (84.1 to 96.7)

No statistical analyses for this end point

Primary: Percentage of Subjects With >=4-Fold Rise in Antibody Titers Against Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or With Other Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11

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End point title

Percentage of Subjects With >=4-Fold Rise in Antibody Titers Against Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or With Other Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11 ^[5] ^[6]

End point description

Antibody titers of Meningococcal Serogroups A, C, Y, and W were measured by hSBA assay. Data for this endpoint was reported for the combined population of Groups 1 and 10, Groups 2 and 11. Analysis was performed on PPAS. Data for this endpoint were not planned to be collected and analysed for Groups 3, 6, 9, and 12.

End point type

Primary

End point timeframe

Day 0 up to Day 30 post-vaccination

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was evaluated for reported arms only.

End point values	Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine	Mexico (Group 5): MenACYW Conjugate Vaccine	Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine	Russian Federation (Group 8): MenACYW Conjugate Vaccine	Groups 1 and10:MenACYW Conjugate Vaccine+MMR+Varicella Vaccine	Groups 2 and 11: MenACYW Conjugate Vaccine
Number of subjects analysed	155	79	196	96	177	87
Units: percentage of subjects
number (confidence interval 95%)
Serogroup A	69.0 (61.1 to 76.2)	70.9 (59.6 to 80.6)	58.2 (50.9 to 65.2)	72.9 (62.9 to 81.5)	82.5 (76.1 to 87.8)	64.4 (53.4 to 74.4)
Serogroup C	100.0 (97.6 to 100.0)	98.7 (93.1 to 100.0)	92.3 (87.7 to 95.7)	91.7 (84.2 to 96.3)	98.3 (95.1 to 99.6)	98.9 (93.8 to 100.0)
Serogroup Y	96.8 (92.6 to 98.9)	94.9 (87.5 to 98.6)	94.4 (90.2 to 97.2)	93.8 (86.9 to 97.7)	95.5 (91.3 to 98.0)	89.7 (81.3 to 95.2)
Serogroup W	86.5 (80.0 to 91.4)	92.4 (84.2 to 97.2)	88.8 (83.5 to 92.8)	90.6 (82.9 to 95.6)	94.9 (90.6 to 97.6)	89.7 (81.3 to 95.2)

No statistical analyses for this end point

Primary: Percentage of Subjects Achieving hSBA Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or Concomitantly With Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11

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End point title

Percentage of Subjects Achieving hSBA Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or Concomitantly With Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11 ^[7] ^[8]

End point description

The hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers >=1:16 for subjects with pre-vaccination titers <1:8 or at least a 4-fold increase in post-vaccination hSBA titers from pre- to post-vaccination, for subjects with pre-vaccination titers >=1:8. Data for this endpoint was reported for the combined population of Groups 1 and 10, Groups 2 and 11. Analysis was performed on PPAS. Data for this endpoint were not planned to be collected and analysed for Groups 3, 6, 9, and 12.

End point type

Primary

End point timeframe

Day 30 post-vaccination

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint is descriptive in nature, no statistical analysis is provided.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was evaluated for reported arms only.

End point values	Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine	Mexico (Group 5): MenACYW Conjugate Vaccine	Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine	Russian Federation (Group 8): MenACYW Conjugate Vaccine	Groups 1 and10:MenACYW Conjugate Vaccine+MMR+Varicella Vaccine	Groups 2 and 11: MenACYW Conjugate Vaccine
Number of subjects analysed	155	79	196	96	177	87
Units: percentage of subjects
number (confidence interval 95%)
Serogroup A	67.1 (59.1 to 74.4)	69.6 (58.2 to 79.5)	56.1 (48.9 to 63.2)	71.9 (61.8 to 80.6)	78.5 (71.7 to 84.3)	63.2 (52.2 to 73.3)
Serogroup C	100.0 (97.6 to 100)	98.7 (93.1 to 100.0)	90.8 (85.9 to 94.5)	91.7 (84.2 to 96.3)	97.7 (94.3 to 99.4)	98.9 (93.8 to 100.0)
Serogroup Y	92.3 (86.9 to 95.9)	87.3 (78.0 to 93.8)	92.9 (88.3 to 96.0)	92.7 (85.6 to 97.0)	93.2 (88.5 to 96.4)	88.5 (79.9 to 94.3)
Serogroup W	82.6 (75.7 to 88.2)	82.3 (72.1 to 90.0)	82.1 (76.1 to 87.2)	90.6 (82.9 to 95.6)	86.4 (80.5 to 91.1)	83.9 (74.5 to 90.9)

No statistical analyses for this end point

Secondary: Geometric Mean Titers of MMR-Varicella Antibodies Following Injection With MMR-Varicella Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 1, 3, 10, and 12

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End point title

Geometric Mean Titers of MMR-Varicella Antibodies Following Injection With MMR-Varicella Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 1, 3, 10, and 12

End point description

Antibodies titers of Measles and Rubella were measured by enzyme immunoassay (EIA). Antibodies titers for mumps and varicella were measured by enzyme-linked immunosorbent assay (ELISA). Data for this endpoint was reported for the combined population of Groups 1 and 10, Groups 3 and 12. Analysis was performed on PPAS. Here, ‘n’ = subjects with available data for each specified category. Data for this endpoint were not planned to be collected and analysed for Groups 2, 4, 5, 6, 7, 8, 9, and 11.

End point type

Secondary

End point timeframe

Day 0 and Day 30 post-vaccination

End point values	Groups 1 and10:MenACYW Conjugate Vaccine+MMR+Varicella Vaccine	Groups 3 and 12: MMR + Varicella Vaccine
Number of subjects analysed	177	92
Units: titers (1/dilution)
geometric mean (confidence interval 95%)
Measles: Day 0 (n=176,92)	40.0 (37.2 to 43.1)	45.0 (40.1 to 50.4)
Measles: Day 30 (n=177,92)	2156 (1893 to 2455)	2840 (2389 to 3378)
Mumps: Day 0 (n=176,92)	5.51 (5.20 to 5.84)	5.43 (5.05 to 5.83)
Mumps: Day 30 (n=177,92)	85.9 (74.7 to 98.7)	97.6 (83.1 to 115)
Rubella: Day 0 (n=176,92)	5.94 (5.32 to 6.63)	7.12 (6.07 to 8.34)
Rubella: Day 30 (n=177,92)	87.6 (79.4 to 96.7)	104 (91.2 to 118)
Varicella: Day 0 (n=176,92)	0.556 (0.484 to 0.638)	0.665 (0.508 to 0.869)
Varicella: Day 30 (n=177,92)	13.4 (11.6 to 15.4)	17.4 (15.2 to 19.9)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Immune Response Following Injection With MMR-Varicella Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 1, 3, 10, and 12

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End point title

Percentage of Subjects With Immune Response Following Injection With MMR-Varicella Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 1, 3, 10, and 12

End point description

Immune response for MMR-Varicella vaccine was defined as: anti-measles Antibody (Ab) concentrations >=255 milli-international unit per milliliter (mIU/mL), anti-mumps Ab concentrations: >=10 Ab units/mL, anti-rubella Ab concentrations >=10 international unit per milliliter (IU/mL),anti-varicella Ab concentrations >=5 glycoprotein enzyme-linked immunosorbent assay (gpELISA) Ab units/mL. Data for this endpoint was planned to be analysed and reported for the combined population of Groups 1 and 10, Groups 3 and 12. Analysis was performed on PPAS. Here, ‘n’ = subjects with available data for each specified category. Data for this endpoint were not planned to be collected and analysed for Groups 2, 4, 5, 6, 7, 8, 9, and 11.

End point type

Secondary

End point timeframe

Day 0 and Day 30 post-vaccination

End point values	Groups 1 and10:MenACYW Conjugate Vaccine+MMR+Varicella Vaccine	Groups 3 and 12: MMR + Varicella Vaccine
Number of subjects analysed	177	92
Units: percentage of subjects
number (confidence interval 95%)
Measles: Day 0 (n=176,92)	0.6 (0.0 to 3.1)	0.0 (0.0 to 3.9)
Measles: Day 30 (n=177,92)	96.6 (92.8 to 98.7)	97.8 (92.4 to 99.7)
Mumps: Day 0 (n=176,92)	7.4 (4.0 to 12.3)	6.5 (2.4 to 13.7)
Mumps: Day 30 (n=177,92)	97.7 (94.3 to 99.4)	100.0 (96.1 to 100.0)
Rubella: Day 0 (n=176,92)	27.3 (20.8 to 34.5)	31.5 (22.2 to 42.0)
Rubella: Day 30 (n=177,92)	100.0 (97.9 to 100)	100.0 (96.1 to 100)
Varicella: Day 0 (n=176,92)	4.0 (1.6 to 8.0)	7.6 (3.1 to 15.1)
Varicella: Day 30 (n=177,92)	93.2 (88.5 to 96.4)	98.9 (94.1 to 100.0)

No statistical analyses for this end point

Secondary: Geometric Mean Titers of Pertussis Toxoid (PT) and Filamentous Hemagglutinin (FHA) Antibodies Following Injection With DTaP-IPV-HB-Hib Vaccine Administrated Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6

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End point title

Geometric Mean Titers of Pertussis Toxoid (PT) and Filamentous Hemagglutinin (FHA) Antibodies Following Injection With DTaP-IPV-HB-Hib Vaccine Administrated Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6 ^[9]

End point description

Antibodies titers of PT and FHA were measured by electrochemiluminescent (ECL) assay. Analysis was performed on PPAS. Data for this endpoint were not planned to be collected and analysed for Groups 1, 2, 3, 5, 7, 8, 9, 10, 11, and 12.

End point type

Secondary

End point timeframe

Day 0 and Day 30 post-vaccination

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was evaluated for reported arms only.

End point values	Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine	Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine
Number of subjects analysed	155	68
Units: titers (1/dilution)
geometric mean (confidence interval 95%)
PT: Day 0	17.9 (15.1 to 21.3)	20.4 (15.3 to 27.0)
PT: Day 30	144 (130 to 159)	169 (144 to 198)
FHA: Day 0	45.5 (37.0 to 55.9)	57.4 (41.4 to 79.5)
FHA: Day 30	299 (265 to 337)	391 (319 to 480)

No statistical analyses for this end point

Secondary: Geometric Mean Titers of DTaP-IPV-HB-Hib Antibodies Following Injection With DTaP-IPV-HB-Hib Administered Alone or Concomitantly With The MenACYW Conjugate Vaccine: Groups 4 and 6

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End point title

Geometric Mean Titers of DTaP-IPV-HB-Hib Antibodies Following Injection With DTaP-IPV-HB-Hib Administered Alone or Concomitantly With The MenACYW Conjugate Vaccine: Groups 4 and 6 ^[10]

End point description

Antibodies titers of Diphtheria, Tetanus and Pertussis were meausured by ECL assay. Antibodies titers of poliovirus types 1, 2, and 3 were measured by neutralization assay. Antibodies titers of Hepatitis B were measured by an immunodiagnostic system using chemiluminescence detection. Antibodies titers of Polyribosyl-ribitol phosphate (PRP) were measured by Farr-type radioimmunoassay (RIA). Analysis was performed on PPAS. Here, ‘n’ = subjects with available data for each specified category. Data for this endpoint were not planned to be collected and analysed for Groups 1, 2, 3, 5, 7, 8, 9, 10, 11, and 12.

End point type

Secondary

End point timeframe

Day 0 (for tetanus only) and Day 30 post-vaccination

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was evaluated for reported arms only.

End point values	Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine	Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine
Number of subjects analysed	155	68
Units: titers (1/dilution)
geometric mean (confidence interval 95%)
Diphtheria: Day 30 (n =155,68)	5.52 (4.94 to 6.17)	6.34 (5.51 to 7.30)
Tetanus: Day 0 (n =155, 67)	0.238 (0.196 to 0.289)	0.234 (0.177 to 0.309)
Tetanus: Day 30 (n =155,68)	7.06 (6.01 to 8.29)	7.11 (5.79 to 8.74)
Polio 1: Day 30 (n=155,68)	4560 (3870 to 5373)	4034 (3052 to 5332)
Polio 2: Day 30 (n=155,68)	7244 (6208 to 8453)	5618 (4578 to 6895)
Polio 3: Day 30 (n=155,68)	5977 (4958 to 7205)	5100 (3840 to 6772)
Hepatitis B: Day 30 (n=155,68)	5171 (4104 to 6515)	7308 (5135 to 10401)
PRP: Day30 (n=155,68)	46.6 (39.6 to 54.9)	56.2 (41.5 to 76.1)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Immune Response Following Injection With DTaP-IPV-HB-Hib Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6

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End point title

Percentage of Subjects With Immune Response Following Injection With DTaP-IPV-HB-Hib Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6 ^[11]

End point description

Immune response for DTaP-IPV-HB-Hib vaccine was defined as: anti-tetanus Ab concentrations: >=0.01 and 0.1 IU/mL at Day 0 and >=0.1 and 1.0 IU/mL at Day 30, anti-diphtheria Ab concentrations: >=0.1 and 1.0 IU/mL, anti-PRP Ab concentrations and >= 0.15 and 1.0 microgram per milliliter (mcg/mL), anti-poliovirus types 1, 2, and 3 Ab titers >=1:8, anti-hepatitis B surface antigen Ab concentrations >=10 mIU/mL, >=100 mIU/mL. Analysis was performed on PPAS. Here, ‘n’ = subjects with available data for each specified category. Data for this endpoint were not planned to be collected and analysed for Groups 1, 2, 3, 5, 7, 8, 9, 10, 11 and 12.

End point type

Secondary

End point timeframe

Day 0 (tetanus only) and Day 30 post-vaccination

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was evaluated for reported arms only.

End point values	Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine	Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine
Number of subjects analysed	155	68
Units: Percentage of subjects
number (confidence interval 95%)
Diphtheria: Day 30 (>=0.1 IU/mL)(n=155,68)	100.0 (97.6 to 100)	100.0 (94.7 to 100)
Diphtheria: Day 30 (>=1 IU/mL) (n=155,68)	98.7 (95.4 to 99.8)	100.0 (94.7 to 100)
Tetanus: Day 0 (>=0.01 IU/mL) (n=155,67)	100.0 (97.6 to 100)	100.0 (94.6 to 100)
Tetanus: Day 0 (>=0.1 IU/mL) (n=155,67)	81.3 (74.2 to 87.1)	77.6 (65.8 to 86.9)
Tetanus: Day 30 (>=0.1 IU/mL) (n=155,68)	100.0 (97.6 to 100)	100.0 (94.7 to 100)
Tetanus: Day 30 (>=1 IU/mL) (n=155,68)	98.1 (94.4 to 99.6)	98.5 (92.1 to 100.0)
Polio 1: Day 30 (>=8 [1/dilution]) (n=155,68)	100.0 (97.6 to 100)	100.0 (94.7 to 100)
Polio 2: Day 30 (>=8 [1/dilution]) (n=155,68)	100.0 (97.6 to 100)	100.0 (94.7 to 100)
Polio 3: Day 30 (>=8 [1/dilution]) (n=155,68)	100.0 (97.6 to 100)	100.0 (94.7 to 100)
Hepatitis B: Day 30 (>=10 mIU/mL) (n=155,68)	100.0 (97.6 to 100)	100.0 (94.7 to 100)
Hepatitis B: Day 30 (>=100 mIU/mL) (n=155,68)	98.7 (95.4 to 99.8)	100.0 (94.7 to 100)
PRP: Day 30 (>=0.15 mcg/mL) (n=155,68)	100.0 (97.6 to 100)	100.0 (94.7 to 100)
PRP: Day 30 (>=1.0 mcg/mL) (n=155,68)	100.0 (97.6 to 100)	100.0 (94.7 to 100)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Vaccine Response of PT and FHA Antibodies Following Injection With DTaP-IPV-HB-Hib Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6

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End point title

Percentage of Subjects With Vaccine Response of PT and FHA Antibodies Following Injection With DTaP-IPV-HB-Hib Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6 ^[12]

End point description

Pertussis and FHA vaccine response was defined as: if the pre-vaccination concentration is < 4 * lower limit of quantification (LLOQ is equal to 2), then the post-vaccination concentration is >=4 * pre-vaccination concentration and if the pre-vaccination concentration is >= 4 * LLOQ, then the post-vaccination concentration is >= 2 * pre-vaccination concentration. Analysis was performed on PPAS. Data for this endpoint were not planned to be collected and analysed for Groups 1, 2, 3, 5, 7, 8, 9, 10, 11, and 12.

End point type

Secondary

End point timeframe

Day 0 and Day 30 post-vaccination

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was evaluated for reported arms only.

End point values	Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine	Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine
Number of subjects analysed	155	68
Units: percentage of subjects
number (confidence interval 95%)
PT: Day 30/Day 0	91.0 (85.3 to 95.0)	92.6 (83.7 to 97.6)
FHA: Day 30/Day 0	89.0 (83.0 to 93.5)	88.2 (78.1 to 94.8)

No statistical analyses for this end point

Secondary: Geometric Mean Titers of PCV13 Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F Antibodies Following Injection With PCV13 Vaccine Administrated Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 7 and 9

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End point title

Geometric Mean Titers of PCV13 Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F Antibodies Following Injection With PCV13 Vaccine Administrated Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 7 and 9 ^[13]

End point description

Antibodies of pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F were measured by ECL assay. Analysis was performed on PPAS. Here, ‘n’ = subjects with available data for each specified category. Data for this endpoint were not planned to be collected and analysed for Groups 1, 2, 3, 4, 5, 6, 8, 10, 11, and 12.

End point type

Secondary

End point timeframe

Day 0 and Day 30 post-vaccination

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was evaluated for reported arms only.

End point values	Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine	Russian Federation (Group 9): PCV13 Vaccine
Number of subjects analysed	196	92
Units: titers (1/dilution)
geometric mean (confidence interval 95%)
Serotype 1: Day 0 (n=193,92)	0.867 (0.741 to 1.01)	0.918 (0.713 to 1.18)
Serotype 1: Day 30 (n=191,92)	2.33 (1.98 to 2.75)	2.14 (1.63 to 2.81)
Serotype 3: Day 0 (n=193,92)	0.409 (0.341 to 0.491)	0.414 (0.322 to 0.533)
Serotype 3: Day 30 (n=191,92)	0.802 (0.664 to 0.967)	0.773 (0.608 to 0.983)
Serotype 4: Day 0 (n=193,92)	0.604 (0.511 to 0.715)	0.653 (0.507 to 0.840)
Serotype 4: Day 30 (n=191,92)	1.97 (1.68 to 2.31)	1.49 (1.15 to 1.93)
Serotype 5: Day 0 (n=193,92)	0.828 (0.719 to 0.953)	0.782 (0.610 to 1.00)
Serotype 5: Day 30 (n=191,92)	1.99 (1.70 to 2.31)	1.73 (1.33 to 2.24)
Serotype 6A: Day 0 (n=193,92)	1.61 (1.33 to 1.95)	1.48 (1.09 to 2.00)
Serotype 6A: Day 30 (n=191,92)	5.96 (4.99 to 7.13)	6.13 (4.47 to 8.41)
Serotype 6B: Day 0 (n=193,92)	0.895 (0.715 to 1.12)	0.691 (0.514 to 0.929)
Serotype 6B: Day 30 (n=191,92)	3.66 (2.99 to 4.50)	2.57 (1.83 to 3.61)
Serotype 7F: Day 0 (n=193,92)	1.32 (1.12 to 1.55)	1.39 (1.08 to 1.77)
Serotype 7F: Day 30 (n=191,92)	3.05 (2.59 to 3.58)	2.67 (2.05 to 3.47)
Serotype 9V: Day 0 (n=193,92)	0.841 (0.710 to 0.997)	0.863 (0.660 to 1.13)
Serotype 9V: Day 30 (n=191,92)	2.34 (1.95 to 2.81)	2.52 (1.92 to 3.30)
Serotype 14: Day 0 (n=192,92)	3.25 (2.74 to 3.86)	3.00 (2.30 to 3.91)
Serotype 14: Day 30 (n=191,92)	7.62 (6.56 to 8.83)	6.30 (5.00 to 7.93)
Serotype 18C: Day 0 (n=193,92)	0.737 (0.620 to 0.876)	0.995 (0.766 to 1.29)
Serotype 18C: Day 30 (n=191,92)	2.19 (1.87 to 2.58)	2.21 (1.73 to 2.83)
Serotype 19A: Day 0 (n=193,92)	1.65 (1.36 to 2.01)	1.96 (1.46 to 2.64)
Serotype 19A: Day 30 (n=191,92)	5.75 (4.85 to 6.80)	5.91 (4.54 to 7.69)
Serotype 19F: Day 0 (n=193,92)	1.78 (1.43 to 2.21)	1.74 (1.28 to 2.35)
Serotype 19F: Day 30 (n=191,92)	5.58 (4.57 to 6.81)	5.53 (3.98 to 7.69)
Serotype 23F: Day 0 (n=192,92)	0.631 (0.519 to 0.768)	0.733 (0.537 to 1.00)
Serotype 23F: Day 30 (n=191,92)	2.42 (2.04 to 2.86)	2.58 (1.98 to 3.37)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Immune Response Following Injection With PCV13 Vaccine Administered Alone or Concomitantly With The MenACYW Conjugate Vaccine: Groups 7 and 9

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End point title

Percentage of Subjects With Immune Response Following Injection With PCV13 Vaccine Administered Alone or Concomitantly With The MenACYW Conjugate Vaccine: Groups 7 and 9 ^[14]

End point description

Immune response for PCV13 for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F was defined as antibodies concentrations >=0.35 mcg/mL or >=1.0 mcg/mL. Analysis was performed on PPAS. Here, ‘n’ = subjects with available data for each specified category. Data for this endpoint were not planned to be collected and analysed for Groups 1, 2, 3, 4, 5, 6, 8, 10, 11, and 12.

End point type

Secondary

End point timeframe

Day 0 and Day 30 post-vaccination

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was evaluated for reported arms only.

End point values	Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine	Russian Federation (Group 9): PCV13 Vaccine
Number of subjects analysed	196	92
Units: percentage of subjects
number (confidence interval 95%)
Serotype 1: Day 0 (>=0.35 mcg/mL)(n=193,92)	80.8 (74.6 to 86.1)	79.3 (69.6 to 87.1)
Serotype 1: Day 0 (>=1.0 mcg/mL) (n=193,92)	43.0 (35.9 to 50.3)	45.7 (35.2 to 56.4)
Serotype 1: Day 30 (>=0.35 mcg/mL) (n=191,92)	97.4 (94.0 to 99.1)	94.6 (87.8 to 98.2)
Serotype 1: Day 30 (>=1.0 mcg/mL) (n=191,92)	76.4 (69.8 to 82.3)	70.7 (60.2 to 79.7)
Serotype 3: Day 0 (>=0.35 mcg/mL) (n=193,92)	49.2 (42.0 to 56.5)	53.3 (42.6 to 63.7)
Serotype 3: Day 0 (>=1.0 mcg/mL) (n=193,92)	22.3 (16.6 to 28.8)	18.5 (11.1 to 27.9)
Serotype 3: Day 30 (>=0.35 mcg/mL) (n=191,92)	72.3 (65.3 to 78.5)	76.1 (66.1 to 84.4)
Serotype 3: Day 30 (>=1.0 mcg/mL) (n=191,92)	48.2 (40.9 to 55.5)	38.0 (28.1 to 48.8)
Serotype 4: Day 0 (>=0.35 mcg/mL) (n=193,92)	66.8 (59.7 to 73.4)	68.5 (58.0 to 77.8)
Serotype 4: Day 0 (>=1.0 mcg/mL) (n=193,92)	33.7 (27.1 to 40.8)	38.0 (28.1 to 48.8)
Serotype 4: Day 30 (>=0.35 mcg/mL) (n=191,92)	92.7 (88.0 to 95.9)	90.2 (82.2 to 95.4)
Serotype 4: Day 30 (>=1.0 mcg/mL) (n=191,92)	80.1 (73.7 to 85.5)	62.0 (51.2 to 71.9)
Serotype 5: Day 0 (>=0.35 mcg/mL) (n=193,92)	81.3 (75.1 to 86.6)	76.1 (66.1 to 84.4)
Serotype 5: Day 0 (>=1.0 mcg/mL) (n=193,92)	41.5 (34.4 to 48.7)	50.0 (39.4 to 60.6)
Serotype 5: Day 30 (>=0.35 mcg/mL) (n=191,92)	94.8 (90.6 to 97.5)	90.2 (82.2 to 95.4)
Serotype 5: Day 30 (>=1.0 mcg/mL) (n=191,92)	71.2 (64.2 to 77.5)	69.6 (59.1 to 78.7)
Serotype 6A: Day 0 (>=0.35 mcg/mL) (n=193,92)	90.2 (85.1 to 94.0)	82.6 (73.3 to 89.7)
Serotype 6A: Day 0 (>=1.0 mcg/mL) (n=193,92)	63.7 (56.5 to 70.5)	65.2 (54.6 to 74.9)
Serotype 6A: Day 30 (>=0.35 mcg/mL) (n=191,92)	97.4 (94.0 to 99.1)	96.7 (90.8 to 99.3)
Serotype 6A: Day 30 (>=1.0 mcg/mL) (n=191,92)	96.3 (92.6 to 98.5)	90.2 (82.2 to 95.4)
Serotype 6B: Day 0 (>=0.35 mcg/mL) (n=193,92)	72.0 (65.1 to 78.2)	68.5 (58.0 to 77.8)
Serotype 6B: Day 0 (>=1.0 mcg/mL) (n=193,92)	44.6 (37.4 to 51.9)	41.3 (31.1 to 52.1)
Serotype 6B: Day 30 (>=0.35 mcg/mL) (n=191,92)	94.8 (90.6 to 97.5)	92.4 (84.9 to 96.9)
Serotype 6B: Day 30 (>=1.0 mcg/mL) (n=191,92)	86.4 (80.7 to 90.9)	75.0 (64.9 to 83.4)
Serotype 7F: Day 0 (>=0.35 mcg/mL) (n=193,92)	87.0 (81.5 to 91.4)	88.0 (79.6 to 93.9)
Serotype 7F: Day 0 (>=1.0 mcg/mL) (n=193,92)	62.7 (55.5 to 69.5)	65.2 (54.6 to 74.9)
Serotype 7F: Day 30 (>=0.35 mcg/mL) (n=191,92)	98.4 (95.5 to 99.7)	94.6 (87.8 to 98.2)
Serotype 7F: Day 30 (>=1.0 mcg/mL) (n=191,92)	80.1 (73.7 to 85.5)	83.7 (74.5 to 90.6)
Serotype 9V: Day 0 (>=0.35 mcg/mL) (n=193,92)	77.2 (70.6 to 82.9)	79.3 (69.6 to 87.1)
Serotype 9V: Day 0 (>=1.0 mcg/mL) (n=193,92)	42.0 (34.9 to 49.3)	43.5 (33.2 to 54.2)
Serotype 9V: Day 30 (>=0.35 mcg/mL) (n=191,92)	95.3 (91.2 to 97.8)	92.4 (84.9 to 96.9)
Serotype 9V: Day 30 (>=1.0 mcg/mL) (n=191,92)	74.3 (67.5 to 80.4)	75.0 (64.9 to 83.4)
Serotype 14: Day 0 (>=0.35 mcg/mL) (n=192,92)	95.8 (92.0 to 98.2)	92.4 (84.9 to 96.9)
Serotype 14: Day 0 (>=1.0 mcg/mL) (n=192,92)	83.3 (77.3 to 88.3)	87.0 (78.0 to 93.1)
Serotype 14: Day 30 (>=0.35 mcg/mL) (n=191,92)	99.0 (96.3 to 99.9)	98.9 (94.1 to 100.0)
Serotype 14: Day 30 (>=1.0 mcg/mL) (n=191,92)	97.4 (94.0 to 99.1)	94.6 (87.8 to 98.2)
Serotype 18C: Day 0 (>=0.35 mcg/mL) (n=193,92)	71.5 (64.6 to 77.8)	84.8 (75.8 to 91.4)
Serotype 18C: Day 0 (>=1.0 mcg/mL) (n=193,92)	40.9 (33.9 to 48.2)	48.9 (38.3 to 59.6)
Serotype 18C: Day 30 (>=0.35 mcg/mL) (n=191,92)	95.3 (91.2 to 97.8)	92.4 (84.9 to 96.9)
Serotype 18C: Day 30 (>=1.0 mcg/mL) (n=191,92)	79.1 (72.6 to 84.6)	79.3 (69.6 to 87.1)
Serotype 19A: Day 0 (>=0.35 mcg/mL) (n=193,92)	87.0 (81.5 to 91.4)	87.0 (78.3 to 93.1)
Serotype 19A: Day 0 (>=1.0 mcg/mL) (n=193,92)	62.7 (55.5 to 69.5)	69.6 (59.1 to 78.7)
Serotype 19A: Day 30 (>=0.35 mcg/mL) (n=191,92)	96.3 (92.6 to 98.5)	98.9 (94.1 to 100.0)
Serotype 19A: Day 30 (>=1.0 mcg/mL) (n=191,92)	92.7 (88.0 to 95.9)	90.2 (82.2 to 95.4)
Serotype 19F: Day 0 (>=0.35 mcg/mL) (n=193,92)	87.0 (81.5 to 91.4)	89.1 (80.9 to 94.7)
Serotype 19F: Day 0 (>=1.0 mcg/mL) (n=193,92)	64.2 (57.0 to 71.0)	65.2 (54.6 to 74.9)
Serotype 19F: Day 30 (>=0.35 mcg/mL) (n=191,92)	96.9 (93.3 to 98.8)	97.8 (92.4 to 99.7)
Serotype 19F: Day 30 (>=1.0 mcg/mL) (n=191,92)	88.0 (82.5 to 92.2)	85.9 (77.0 to 92.3)
Serotype 23F: Day 0 (>=0.35 mcg/mL) (n=192,92)	68.2 (61.1 to 74.7)	64.1 (53.5 to 73.9)
Serotype 23F: Day 0 (>=1.0 mcg/mL) (n=192,92)	34.9 (28.2 to 42.1)	44.6 (34.2 to 55.3)
Serotype 23F: Day 30 (>=0.35 mcg/mL) (n=191,92)	96.3 (92.6 to 98.5)	93.5 (86.3 to 97.6)
Serotype 23F: Day 30 (>=1.0 mcg/mL) (n=191,92)	72.3 (65.3 to 78.5)	78.3 (68.4 to 86.2)

No statistical analyses for this end point

Secondary: Number of Subjects Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, Swelling): Groups 1, 2, 3, 10, 11 and 12

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End point title

Number of Subjects Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, Swelling): Groups 1, 2, 3, 10, 11 and 12 ^[15]

End point description

Solicited injection site reactions: tenderness, erythema and swelling. Tenderness: Grade 3: cries when injected limb moved, or the movement of the injected limb reduced, Erythema and swelling: Grade 3: >= 50 millimeter (mm). Percentage of subjects with any of the Grade and Grade 3 solicited injection-site reactions were reported. Analysis was performed on safety analysis set which included all subjects who received at least 1 dose of study vaccine and had any safety data available. Here, '99999' was used as space fillers and indicate that vaccine was not administered to the specified group.

End point type

Secondary

End point timeframe

Within 7 days post vaccination

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for Groups 4, 5, 6, 7, 8, and 9 are reported in separate endpoints.

End point values	South Korea(Group1): MenACYW Conjugate +MMR+ Varicella Vaccine	South Korea (Group 2): MenACYW Conjugate Vaccine	South Korea (Group 3): MMR + Varicella Vaccine	Thailand (Group 10): MenACYW Conjugate +MMR+Varicella Vaccine	Thailand (Group 11): MenACYW Conjugate Vaccine	Thailand (Group 12): MMR + Varicella Vaccine
Number of subjects analysed	103	52	53	86	42	42
Units: subjects
number (not applicable)
MenACYW: Tenderness: Any Grade	28	15	99999	25	15	99999
MenACYW: Tenderness: Grade 3	1	0	99999	0	1	99999
MenACYW: Erythema: Any Grade	27	20	99999	21	6	99999
MenACYW: Erythema: Grade 3	0	2	99999	0	0	99999
MenACYW: Swelling: Any Grade	18	14	99999	13	5	99999
MenACYW: Swelling: Grade 3	0	0	99999	0	0	99999
MMR: Tenderness: Any Grade	21	99999	10	17	99999	17
MMR: Tenderness: Grade 3	1	99999	0	0	99999	0
MMR: Erythema: Any Grade	13	99999	6	17	99999	6
MMR: Erythema: Grade 3	0	99999	0	0	99999	0
MMR: Swelling: Any Grade	7	99999	1	11	99999	3
MMR: Swelling: Grade 3	0	99999	0	0	99999	0
Varicella: Tenderness: Any Grade	23	99999	11	15	99999	13
Varicella: Tenderness: Grade 3	0	99999	0	0	99999	1
Varicella: Erythema: Any Grade	19	99999	4	13	99999	6
Varicella: Erythema: Grade 3	1	99999	0	0	99999	0
Varicella: Swelling: Any Grade	10	99999	2	11	99999	4
Varicella: Swelling: Grade 3	0	99999	0	0	99999	0

No statistical analyses for this end point

Secondary: Number of Subjects Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, Swelling): Groups 4, 5 and 6

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End point title

Number of Subjects Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, Swelling): Groups 4, 5 and 6 ^[16]

End point description

Solicited injection site reactions: tenderness, erythema and swelling. Tenderness: Grade 3: cries when injected limb moved, or the movement of the injected limb reduced, Erythema and swelling: Grade 3: >= 50 mm. Percentage of subjects with any of the Grade and Grade 3 solicited injection-site reactions were reported. Analysis was performed on safety analysis set. Here, ‘n’ = subjects with available data for each specified category. Here, '99999' was used as space fillers and indicate that vaccine was not administered to the specified group.

End point type

Secondary

End point timeframe

Within 7 days post vaccination

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was evaluated for reported arms only.

End point values	Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine	Mexico (Group 5): MenACYW Conjugate Vaccine	Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine
Number of subjects analysed	200	100	100
Units: subjects
number (not applicable)
MenACYW: Tenderness: Any Grade(n=191,98,100)	68	27	99999
MenACYW: Tenderness: Grade 3 (n=191,98,100)	6	1	99999
MenACYW: Erythema: Any Grade (n=191,98,100)	40	15	99999
MenACYW: Erythema: Grade 3 (n=191,98,100)	3	3	99999
MenACYW: Swelling: Any Grade (n=191,98,100)	23	8	99999
MenACYW: Swelling: Grade 3 (n=191,98,100)	2	2	99999
DTaP-IPV-HB-Hib:Tenderness:Any Grade(n=191,100,95)	80	99999	54
DTaP-IPV-HB-Hib: Tenderness:Grade 3 (n=191,100,95)	6	99999	10
DTaP-IPV-HB-Hib: Erythema:Any Grade (n=191,100,95)	56	99999	37
DTaP-IPV-HB-Hib: Erythema: Grade 3 (n=191,100,95)	8	99999	5
DTaP-IPV-HB-Hib: Swelling:Any Grade (n=191,100,95)	45	99999	30
DTaP-IPV-HB-Hib: Swelling: Grade 3 (n=191,100,95)	8	99999	4

No statistical analyses for this end point

Secondary: Number of Subjects Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, Swelling): Groups 7, 8 and 9

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End point title

Number of Subjects Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, Swelling): Groups 7, 8 and 9 ^[17]

End point description

Solicited injection site reactions: tenderness, erythema and swelling. Tenderness: Grade 3: cries when injected limb moved, or the movement of the injected limb reduced, Erythema and swelling: Grade 3: >= 50 mm. Percentage of subjects with any of the Grade and Grade 3 solicited injection-site reactions were reported. Analysis was performed on Safety analysis set. Here, '99999' was used as space fillers and indicate that vaccine was not administered to the specified group.

End point type

Secondary

End point timeframe

Within 07 days post vaccination

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for Groups 1, 2, 3, 10, 11, 12, 4, 5, and 6 are reported in separate endpoints.

End point values	Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine	Russian Federation (Group 8): MenACYW Conjugate Vaccine	Russian Federation (Group 9): PCV13 Vaccine
Number of subjects analysed	200	100	99
Units: subjects
number (not applicable)
MenACYW: Tenderness: Any Grade	28	8	99999
MenACYW: Tenderness: Grade 3	4	0	99999
MenACYW: Erythema: Any Grade	43	17	99999
MenACYW: Erythema: Grade 3	0	0	99999
MenACYW: Swelling: Any Grade	8	7	99999
MenACYW: Swelling: Grade 3	0	0	99999
PCV13: Tenderness: Any Grade	34	99999	9
PCV13: Tenderness: Grade 3	5	99999	1
PCV13: Erythema: Any Grade	48	99999	8
PCV13: Erythema: Grade 3	0	99999	0
PCV13: Swelling: Any Grade	19	99999	2
PCV13: Swelling: Grade 3	0	99999	0

No statistical analyses for this end point

Secondary: Number of Subjects Reporting at Least One Solicited Systemic Reactions (Fever, Vomiting, Abnormal Crying, Drowsiness, Appetite Loss, Irritability)

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End point title

Number of Subjects Reporting at Least One Solicited Systemic Reactions (Fever, Vomiting, Abnormal Crying, Drowsiness, Appetite Loss, Irritability)

End point description

Solicited systemic reaction: Fever: Grade 3: > 39.5°C, Vomiting: Grade 3: >= 6 episodes per 24 hours or requiring parenteral hydration, Crying abnormal: Grade 3: >3 hours, Drowsiness: Grade 3: sleeping most of the time or difficult to wake up, Appetite lost: Grade 3: refuses >= 3 feeds/meals or refuses most feeds/meals, Irritability: Grade 3: inconsolable. Percentage of subjects with any of the Grade and Grade 3 solicited injection-site reactions were reported. Analysis was performed on Safety analysis set. Here, ‘number of subjects analysed' = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Within 07 days post vaccination

End point values	South Korea(Group1): MenACYW Conjugate +MMR+ Varicella Vaccine	South Korea (Group 2): MenACYW Conjugate Vaccine	South Korea (Group 3): MMR + Varicella Vaccine	Thailand (Group 10): MenACYW Conjugate +MMR+Varicella Vaccine	Thailand (Group 11): MenACYW Conjugate Vaccine	Thailand (Group 12): MMR + Varicella Vaccine	Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine	Mexico (Group 5): MenACYW Conjugate Vaccine	Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine	Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine	Russian Federation (Group 8): MenACYW Conjugate Vaccine	Russian Federation (Group 9): PCV13 Vaccine
Number of subjects analysed	103	52	53	86	42	42	191	98	95	200	100	99
Units: subjects
number (not applicable)
Fever: Any Grade	17	9	5	6	1	3	32	7	16	12	3	2
Fever: Grade 3	1	2	1	0	1	0	4	1	0	0	0	0
Vomiting: Any Grade	6	3	2	5	4	5	15	6	9	0	0	0
Vomiting: Grade 3	0	0	0	0	0	1	0	1	0	0	0	0
Abnormal crying: Any Grade	21	9	6	14	14	12	46	25	26	8	4	2
Abnormal crying: Grade 3	0	0	0	0	0	0	1	1	1	2	0	0
Drowsiness: Any Grade	17	8	9	8	7	7	31	15	17	25	6	4
Drowsiness: Grade 3	0	0	0	0	0	1	1	0	2	1	0	0
Appetite Lost: Any Grade	29	10	8	11	12	5	51	25	20	19	12	7
Appetite Lost: Grade 3	1	0	0	0	0	2	8	2	3	1	0	0
Irritability: Any Grade	31	12	11	14	11	14	64	34	33	26	16	9
Irritability: Grade 3	0	0	0	0	1	0	4	1	3	4	0	0

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse event (AE) data were collected from Day 0 up to Day 30 post-vaccination and solicited reaction (SR) data within 7 days after vaccination.Serious adverse event (SAE) data were collected throughout the study period (up to Day 30 post-vaccination)

Adverse event reporting additional description

Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

South Korea(Group1):MenACYW Conjugate +MMR +Varicella Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine, MMR vaccine, and varicella vaccine on Day 0.

Reporting group title

South Korea (Group 2): MenACYW Conjugate Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Reporting group title

South Korea (Group 3): MMR + Varicella Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MMR vaccine and Varicella vaccine on Day 0.

Reporting group title

Thailand (Group 10):MenACYW Conjugate + MMR+ Varicella Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine, MMR, vaccine and varicella vaccine on Day 0.

Reporting group title

Thailand (Group 11): MenACYW Conjugate Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Reporting group title

Thailand (Group 12): MMR + Varicella Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MMR vaccine and varicella vaccine on Day 0.

Reporting group title

Groups 1 and10:MenACYW Conjugate Vaccine+MMR+Varicella Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) from South Korea and Thailand received single dose of MenACYW Conjugate vaccine, MMR vaccine, and varicella vaccine on Day 0.

Reporting group title

Groups 2 and 11: MenACYW Conjugate Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) from South Korea and Thailand received single dose of MenACYW Conjugate vaccine on Day 0.

Reporting group title

Groups 3 and 12: MMR + Varicella Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) from South Korea and Thailand received single dose of MMR vaccine and varicella vaccine on Day 0.

Reporting group title

Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine and DTaP-IPV-HB-Hib vaccine on Day 0.

Reporting group title

Mexico (Group 5): MenACYW Conjugate Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Reporting group title

Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of DTaP-IPV-HB-Hib Vaccine on Day 0.

Reporting group title

Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 15 to 23 months) received single dose of MenACYW Conjugate vaccine and PCV13 vaccine on Day 0.

Reporting group title

Russian Federation (Group 8): MenACYW Conjugate Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 14 months or 16 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Reporting group title

Russian Federation (Group 9): PCV13 Vaccine

Reporting group description

Healthy, meningococcal-vaccine naïve toddlers (aged 15 to 23 months) received single dose of PCV13 vaccine on Day 0.

South Korea(Group1):MenACYW Conjugate +MMR +Varicella Vaccine

South Korea (Group 2): MenACYW Conjugate Vaccine

South Korea (Group 3): MMR + Varicella Vaccine

Thailand (Group 10):MenACYW Conjugate + MMR+ Varicella Vaccine

Thailand (Group 11): MenACYW Conjugate Vaccine

Thailand (Group 12): MMR + Varicella Vaccine

Groups 1 and10:MenACYW Conjugate Vaccine+MMR+Varicella Vaccine

Groups 2 and 11: MenACYW Conjugate Vaccine

Groups 3 and 12: MMR + Varicella Vaccine

Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine

Mexico (Group 5): MenACYW Conjugate Vaccine

Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine

Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine

Russian Federation (Group 8): MenACYW Conjugate Vaccine

Russian Federation (Group 9): PCV13 Vaccine

Total subjects affected by serious adverse events

subjects affected / exposed

6 / 103 (5.83%)

4 / 52 (7.69%)

2 / 53 (3.77%)

0 / 86 (0.00%)

1 / 42 (2.38%)

0 / 42 (0.00%)

6 / 189 (3.17%)

5 / 94 (5.32%)

2 / 95 (2.11%)

0 / 200 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 99 (0.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

Nervous system disorders

Febrile Convulsion

subjects affected / exposed

0 / 103 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 86 (0.00%)

0 / 42 (0.00%)

0 / 189 (0.00%)

0 / 94 (0.00%)

0 / 95 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 99 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Asthma

subjects affected / exposed

0 / 103 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 86 (0.00%)

0 / 42 (0.00%)

0 / 189 (0.00%)

0 / 94 (0.00%)

0 / 95 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

1 / 100 (1.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 99 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Bronchiolitis

subjects affected / exposed

0 / 103 (0.00%)

2 / 52 (3.85%)

0 / 53 (0.00%)

0 / 86 (0.00%)

0 / 42 (0.00%)

0 / 189 (0.00%)

2 / 94 (2.13%)

0 / 95 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 99 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchitis

subjects affected / exposed

0 / 103 (0.00%)

1 / 52 (1.92%)

0 / 53 (0.00%)

0 / 86 (0.00%)

0 / 42 (0.00%)

0 / 189 (0.00%)

1 / 94 (1.06%)

0 / 95 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 99 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchitis Viral

subjects affected / exposed

2 / 103 (1.94%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 86 (0.00%)

0 / 42 (0.00%)

2 / 189 (1.06%)

0 / 94 (0.00%)

0 / 95 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 99 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Croup Infectious

subjects affected / exposed

0 / 103 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 86 (0.00%)

1 / 42 (2.38%)

0 / 42 (0.00%)

0 / 189 (0.00%)

1 / 94 (1.06%)

0 / 95 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 99 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis

subjects affected / exposed

1 / 103 (0.97%)

1 / 52 (1.92%)

0 / 53 (0.00%)

0 / 86 (0.00%)

0 / 42 (0.00%)

1 / 189 (0.53%)

1 / 94 (1.06%)

0 / 95 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 99 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hand-Foot-And-Mouth Disease

subjects affected / exposed

1 / 103 (0.97%)

1 / 52 (1.92%)

0 / 53 (0.00%)

0 / 86 (0.00%)

0 / 42 (0.00%)

1 / 189 (0.53%)

1 / 94 (1.06%)

0 / 95 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 99 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Otitis Media Viral

subjects affected / exposed

0 / 103 (0.00%)

0 / 52 (0.00%)

1 / 53 (1.89%)

0 / 86 (0.00%)

0 / 42 (0.00%)

0 / 189 (0.00%)

0 / 94 (0.00%)

1 / 95 (1.05%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 99 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia Viral

subjects affected / exposed

0 / 103 (0.00%)

0 / 52 (0.00%)

1 / 53 (1.89%)

0 / 86 (0.00%)

0 / 42 (0.00%)

0 / 189 (0.00%)

0 / 94 (0.00%)

1 / 95 (1.05%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 99 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory Syncytial Virus Bronchiolitis

subjects affected / exposed

1 / 103 (0.97%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 86 (0.00%)

0 / 42 (0.00%)

1 / 189 (0.53%)

0 / 94 (0.00%)

0 / 95 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 99 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tonsillitis

subjects affected / exposed

1 / 103 (0.97%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 86 (0.00%)

0 / 42 (0.00%)

1 / 189 (0.53%)

0 / 94 (0.00%)

0 / 95 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 200 (0.00%)

0 / 100 (0.00%)

0 / 99 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	South Korea(Group1):MenACYW Conjugate +MMR +Varicella Vaccine	South Korea (Group 2): MenACYW Conjugate Vaccine	South Korea (Group 3): MMR + Varicella Vaccine	Thailand (Group 10):MenACYW Conjugate + MMR+ Varicella Vaccine	Thailand (Group 11): MenACYW Conjugate Vaccine	Thailand (Group 12): MMR + Varicella Vaccine	Groups 1 and10:MenACYW Conjugate Vaccine+MMR+Varicella Vaccine	Groups 2 and 11: MenACYW Conjugate Vaccine	Groups 3 and 12: MMR + Varicella Vaccine	Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine	Mexico (Group 5): MenACYW Conjugate Vaccine	Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine	Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine	Russian Federation (Group 8): MenACYW Conjugate Vaccine	Russian Federation (Group 9): PCV13 Vaccine
Total subjects affected by non serious adverse events
subjects affected / exposed	85 / 103 (82.52%)	43 / 52 (82.69%)	37 / 53 (69.81%)	52 / 86 (60.47%)	33 / 42 (78.57%)	34 / 42 (80.95%)	137 / 189 (72.49%)	76 / 94 (80.85%)	71 / 95 (74.74%)	142 / 200 (71.00%)	65 / 100 (65.00%)	85 / 100 (85.00%)	75 / 200 (37.50%)	30 / 100 (30.00%)	17 / 99 (17.17%)
Nervous system disorders
Somnolence
subjects affected / exposed	17 / 103 (16.50%)	8 / 52 (15.38%)	9 / 53 (16.98%)	8 / 86 (9.30%)	7 / 42 (16.67%)	7 / 42 (16.67%)	25 / 189 (13.23%)	15 / 94 (15.96%)	16 / 95 (16.84%)	31 / 200 (15.50%)	15 / 100 (15.00%)	17 / 100 (17.00%)	25 / 200 (12.50%)	6 / 100 (6.00%)	4 / 99 (4.04%)
occurrences all number	17	8	9	8	7	7	25	15	16	31	15	17	25	6	4
General disorders and administration site conditions
Crying
subjects affected / exposed	21 / 103 (20.39%)	9 / 52 (17.31%)	6 / 53 (11.32%)	15 / 86 (17.44%)	14 / 42 (33.33%)	12 / 42 (28.57%)	36 / 189 (19.05%)	23 / 94 (24.47%)	18 / 95 (18.95%)	46 / 200 (23.00%)	25 / 100 (25.00%)	26 / 100 (26.00%)	8 / 200 (4.00%)	4 / 100 (4.00%)	2 / 99 (2.02%)
occurrences all number	21	9	6	15	14	12	36	23	18	46	25	26	8	4	2
Injection Site Erythema
subjects affected / exposed	35 / 103 (33.98%)	20 / 52 (38.46%)	8 / 53 (15.09%)	22 / 86 (25.58%)	6 / 42 (14.29%)	7 / 42 (16.67%)	57 / 189 (30.16%)	26 / 94 (27.66%)	15 / 95 (15.79%)	67 / 200 (33.50%)	15 / 100 (15.00%)	37 / 100 (37.00%)	55 / 200 (27.50%)	17 / 100 (17.00%)	8 / 99 (8.08%)
occurrences all number	60	20	10	51	6	12	111	26	22	96	15	37	91	17	8
Injection Site Pain
subjects affected / exposed	31 / 103 (30.10%)	15 / 52 (28.85%)	12 / 53 (22.64%)	26 / 86 (30.23%)	15 / 42 (35.71%)	18 / 42 (42.86%)	57 / 189 (30.16%)	30 / 94 (31.91%)	30 / 95 (31.58%)	87 / 200 (43.50%)	27 / 100 (27.00%)	54 / 100 (54.00%)	37 / 200 (18.50%)	8 / 100 (8.00%)	9 / 99 (9.09%)
occurrences all number	72	15	21	57	15	30	129	30	51	148	27	54	62	8	9
Injection Site Swelling
subjects affected / exposed	25 / 103 (24.27%)	14 / 52 (26.92%)	3 / 53 (5.66%)	15 / 86 (17.44%)	5 / 42 (11.90%)	4 / 42 (9.52%)	40 / 189 (21.16%)	19 / 94 (20.21%)	7 / 95 (7.37%)	52 / 200 (26.00%)	8 / 100 (8.00%)	30 / 100 (30.00%)	21 / 200 (10.50%)	7 / 100 (7.00%)	2 / 99 (2.02%)
occurrences all number	35	14	3	35	5	7	70	19	10	68	8	30	27	7	2
Pyrexia
subjects affected / exposed	21 / 103 (20.39%)	11 / 52 (21.15%)	10 / 53 (18.87%)	6 / 86 (6.98%)	3 / 42 (7.14%)	4 / 42 (9.52%)	27 / 189 (14.29%)	14 / 94 (14.89%)	14 / 95 (14.74%)	35 / 200 (17.50%)	8 / 100 (8.00%)	17 / 100 (17.00%)	13 / 200 (6.50%)	3 / 100 (3.00%)	2 / 99 (2.02%)
occurrences all number	21	12	12	6	3	4	27	15	16	35	8	17	13	3	3
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	3 / 103 (2.91%)	2 / 52 (3.85%)	0 / 53 (0.00%)	1 / 86 (1.16%)	0 / 42 (0.00%)	0 / 42 (0.00%)	4 / 189 (2.12%)	2 / 94 (2.13%)	0 / 95 (0.00%)	12 / 200 (6.00%)	5 / 100 (5.00%)	6 / 100 (6.00%)	0 / 200 (0.00%)	1 / 100 (1.00%)	0 / 99 (0.00%)
occurrences all number	3	2	0	1	0	0	4	2	0	13	6	6	0	1	0
Vomiting
subjects affected / exposed	7 / 103 (6.80%)	3 / 52 (5.77%)	2 / 53 (3.77%)	6 / 86 (6.98%)	4 / 42 (9.52%)	6 / 42 (14.29%)	13 / 189 (6.88%)	7 / 94 (7.45%)	8 / 95 (8.42%)	16 / 200 (8.00%)	7 / 100 (7.00%)	9 / 100 (9.00%)	0 / 200 (0.00%)	0 / 100 (0.00%)	0 / 99 (0.00%)
occurrences all number	7	3	2	6	4	6	13	7	8	17	7	9	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	3 / 103 (2.91%)	0 / 52 (0.00%)	5 / 53 (9.43%)	0 / 86 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	3 / 189 (1.59%)	0 / 94 (0.00%)	5 / 95 (5.26%)	5 / 200 (2.50%)	3 / 100 (3.00%)	2 / 100 (2.00%)	1 / 200 (0.50%)	1 / 100 (1.00%)	0 / 99 (0.00%)
occurrences all number	3	0	5	0	0	0	3	0	5	5	3	2	1	1	0
Rhinorrhoea
subjects affected / exposed	1 / 103 (0.97%)	3 / 52 (5.77%)	4 / 53 (7.55%)	0 / 86 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 189 (0.53%)	3 / 94 (3.19%)	4 / 95 (4.21%)	1 / 200 (0.50%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 200 (0.00%)	0 / 100 (0.00%)	0 / 99 (0.00%)
occurrences all number	1	3	4	0	0	0	1	3	4	1	0	1	0	0	0
Psychiatric disorders
Irritability
subjects affected / exposed	31 / 103 (30.10%)	12 / 52 (23.08%)	11 / 53 (20.75%)	14 / 86 (16.28%)	11 / 42 (26.19%)	14 / 42 (33.33%)	45 / 189 (23.81%)	23 / 94 (24.47%)	25 / 95 (26.32%)	64 / 200 (32.00%)	34 / 100 (34.00%)	33 / 100 (33.00%)	26 / 200 (13.00%)	16 / 100 (16.00%)	9 / 99 (9.09%)
occurrences all number	31	12	11	15	11	14	46	23	25	64	34	33	26	16	9
Infections and infestations
Bronchitis
subjects affected / exposed	4 / 103 (3.88%)	1 / 52 (1.92%)	4 / 53 (7.55%)	1 / 86 (1.16%)	0 / 42 (0.00%)	1 / 42 (2.38%)	5 / 189 (2.65%)	1 / 94 (1.06%)	5 / 95 (5.26%)	0 / 200 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	1 / 200 (0.50%)	0 / 100 (0.00%)	1 / 99 (1.01%)
occurrences all number	4	1	5	1	0	1	5	1	6	0	0	0	1	0	1
Nasopharyngitis
subjects affected / exposed	29 / 103 (28.16%)	17 / 52 (32.69%)	13 / 53 (24.53%)	5 / 86 (5.81%)	3 / 42 (7.14%)	6 / 42 (14.29%)	34 / 189 (17.99%)	20 / 94 (21.28%)	19 / 95 (20.00%)	29 / 200 (14.50%)	18 / 100 (18.00%)	15 / 100 (15.00%)	2 / 200 (1.00%)	1 / 100 (1.00%)	0 / 99 (0.00%)
occurrences all number	37	23	18	5	4	7	42	27	25	31	18	16	2	1	0
Pharyngitis
subjects affected / exposed	1 / 103 (0.97%)	2 / 52 (3.85%)	3 / 53 (5.66%)	2 / 86 (2.33%)	1 / 42 (2.38%)	2 / 42 (4.76%)	3 / 189 (1.59%)	3 / 94 (3.19%)	5 / 95 (5.26%)	9 / 200 (4.50%)	6 / 100 (6.00%)	4 / 100 (4.00%)	0 / 200 (0.00%)	0 / 100 (0.00%)	0 / 99 (0.00%)
occurrences all number	1	2	4	2	1	2	3	3	6	9	6	4	0	0	0
Rhinitis
subjects affected / exposed	0 / 103 (0.00%)	1 / 52 (1.92%)	0 / 53 (0.00%)	0 / 86 (0.00%)	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 189 (0.00%)	1 / 94 (1.06%)	1 / 95 (1.05%)	0 / 200 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	3 / 200 (1.50%)	6 / 100 (6.00%)	1 / 99 (1.01%)
occurrences all number	0	1	0	0	0	1	0	1	1	0	0	0	3	6	1
Upper Respiratory Tract Infection
subjects affected / exposed	6 / 103 (5.83%)	3 / 52 (5.77%)	0 / 53 (0.00%)	3 / 86 (3.49%)	2 / 42 (4.76%)	4 / 42 (9.52%)	9 / 189 (4.76%)	5 / 94 (5.32%)	4 / 95 (4.21%)	6 / 200 (3.00%)	1 / 100 (1.00%)	0 / 100 (0.00%)	0 / 200 (0.00%)	0 / 100 (0.00%)	0 / 99 (0.00%)
occurrences all number	7	3	0	3	2	4	10	5	4	6	1	0	0	0	0
Metabolism and nutrition disorders
Decreased Appetite
subjects affected / exposed	29 / 103 (28.16%)	10 / 52 (19.23%)	8 / 53 (15.09%)	11 / 86 (12.79%)	12 / 42 (28.57%)	5 / 42 (11.90%)	40 / 189 (21.16%)	22 / 94 (23.40%)	13 / 95 (13.68%)	51 / 200 (25.50%)	25 / 100 (25.00%)	20 / 100 (20.00%)	19 / 200 (9.50%)	12 / 100 (12.00%)	7 / 99 (7.07%)
occurrences all number	29	10	8	11	12	5	40	22	13	51	25	20	19	12	7

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Were there any global substantial amendments to the protocol? Yes

11 Jul 2016

Following amendment changes were made: Identified the Coordinating Investigator for each country, provided available Health Authority file numbers and update of Regional Clinical Trial Manager information; revised to anticipate the need to potentially include additional sites in South Korea; Visit 0 including activities performed were added for subjects in the Russian Federation; primary endpoint measurement was changed so that it was measured by hSBA instead of rSBA and the definition of hSBA in the primary objective was updated; included screening criteria for the subjects in the Russian Federation; neurological examinations were added according to the recommendations of Russian Health Authorities; updated the planned trial calendar; provided specific labeling information; and updated wording so that Abs to diphtheria, inactivated polio, hepatitis B and Haemophilus influenzae antigens would not be measured before vaccination.

05 May 2017

Following amendment changes were made: Updated to expand the age range of toddlers in Russia who were eligible to receive the 3rd dose of PCV13 vaccine as part of the Russian National Immunization program; specified for pertussis antigens; clarified timing of the 2nd dose of PCV13; included hepatitis B Ab level threshold of 100 mIU/mL for reliable prediction of long-term protection against hepatitis B virus; clarified that only tetanus and pertussis antigens would be tested before and 30 days after vaccination; and defined the end of the trail period as when the last assay results were available and updated trial calendar.

11 Sep 2017

Following amendment changes were made: Updated protocol to include Thailand as well as information pertaining to Thailand (including but not limited to Principal Investigators, number of sites, number of subjects planned to be enrolled, age of subjects, reporting requirements for SAEs in Thailand) as the study would also be conducted there; updated the number of subjects planned to be enrolled in South Korea; clarified the number of subjects in each group that would have the Ab responses to the meningococcal serogroups A, C, Y, and W measured by rSBA for the observational objective; specified the serostatus cutoffs for Abs to the antigens contained in MMR vaccine and Varicella vaccine based on the assays that were to be used for the analysis;and updated the definition of pertussis vaccine response specific for the booster vaccination response in order to make the definition specific to the manner the vaccine was being used in the study.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Other Pediatric Vaccines in Healthy Toddlers

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Geometric Mean Titers of MenACYW Antibodies Following Injection With MenACYW Conjugate Vaccine Administered Alone or Concomitantly With Other Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11

Primary: Geometric Mean Titers of MenACYW Antibodies Following Injection With MenACYW Conjugate Vaccine Administered Alone or Concomitantly With Other Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11

Primary: Percentage of Subjects With Antibody Titers >=1:4 and 1:8 Against Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or With Other Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11

Primary: Percentage of Subjects With Antibody Titers >=1:4 and 1:8 Against Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or With Other Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11

Primary: Percentage of Subjects With >=4-Fold Rise in Antibody Titers Against Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or With Other Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11

Primary: Percentage of Subjects With >=4-Fold Rise in Antibody Titers Against Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or With Other Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11

Primary: Percentage of Subjects Achieving hSBA Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or Concomitantly With Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11

Primary: Percentage of Subjects Achieving hSBA Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or Concomitantly With Paediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11

Secondary: Geometric Mean Titers of MMR-Varicella Antibodies Following Injection With MMR-Varicella Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 1, 3, 10, and 12

Secondary: Geometric Mean Titers of MMR-Varicella Antibodies Following Injection With MMR-Varicella Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 1, 3, 10, and 12

Secondary: Percentage of Subjects With Immune Response Following Injection With MMR-Varicella Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 1, 3, 10, and 12

Secondary: Percentage of Subjects With Immune Response Following Injection With MMR-Varicella Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 1, 3, 10, and 12

Secondary: Geometric Mean Titers of Pertussis Toxoid (PT) and Filamentous Hemagglutinin (FHA) Antibodies Following Injection With DTaP-IPV-HB-Hib Vaccine Administrated Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6

Secondary: Geometric Mean Titers of Pertussis Toxoid (PT) and Filamentous Hemagglutinin (FHA) Antibodies Following Injection With DTaP-IPV-HB-Hib Vaccine Administrated Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6

Secondary: Geometric Mean Titers of DTaP-IPV-HB-Hib Antibodies Following Injection With DTaP-IPV-HB-Hib Administered Alone or Concomitantly With The MenACYW Conjugate Vaccine: Groups 4 and 6

Secondary: Geometric Mean Titers of DTaP-IPV-HB-Hib Antibodies Following Injection With DTaP-IPV-HB-Hib Administered Alone or Concomitantly With The MenACYW Conjugate Vaccine: Groups 4 and 6

Secondary: Percentage of Subjects With Immune Response Following Injection With DTaP-IPV-HB-Hib Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6

Secondary: Percentage of Subjects With Immune Response Following Injection With DTaP-IPV-HB-Hib Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6

Secondary: Percentage of Subjects With Vaccine Response of PT and FHA Antibodies Following Injection With DTaP-IPV-HB-Hib Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6

Secondary: Percentage of Subjects With Vaccine Response of PT and FHA Antibodies Following Injection With DTaP-IPV-HB-Hib Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6

Secondary: Geometric Mean Titers of PCV13 Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F Antibodies Following Injection With PCV13 Vaccine Administrated Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 7 and 9

Secondary: Geometric Mean Titers of PCV13 Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F Antibodies Following Injection With PCV13 Vaccine Administrated Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 7 and 9

Secondary: Percentage of Subjects With Immune Response Following Injection With PCV13 Vaccine Administered Alone or Concomitantly With The MenACYW Conjugate Vaccine: Groups 7 and 9

Secondary: Percentage of Subjects With Immune Response Following Injection With PCV13 Vaccine Administered Alone or Concomitantly With The MenACYW Conjugate Vaccine: Groups 7 and 9

Secondary: Number of Subjects Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, Swelling): Groups 1, 2, 3, 10, 11 and 12

Secondary: Number of Subjects Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, Swelling): Groups 1, 2, 3, 10, 11 and 12

Secondary: Number of Subjects Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, Swelling): Groups 4, 5 and 6

Secondary: Number of Subjects Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, Swelling): Groups 4, 5 and 6

Secondary: Number of Subjects Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, Swelling): Groups 7, 8 and 9

Secondary: Number of Subjects Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, Swelling): Groups 7, 8 and 9

Secondary: Number of Subjects Reporting at Least One Solicited Systemic Reactions (Fever, Vomiting, Abnormal Crying, Drowsiness, Appetite Loss, Irritability)

Secondary: Number of Subjects Reporting at Least One Solicited Systemic Reactions (Fever, Vomiting, Abnormal Crying, Drowsiness, Appetite Loss, Irritability)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Other Pediatric Vaccines in Healthy Toddlers