Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Toddlers

• Sponsor: Sanofi Pasteur, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02955797
• Collaborator: (none)
• Enrollment: 918
• Locations: 33
• Arms: 4
• Actual Duration (Months): 8
• Patients Per Site: 27.8
• Patients Per Site Per Month: 3.5

Study Details

Study Description

Brief Summary

The purpose of the study was to evaluate the immunogenicity and describe the safety of a single dose of Meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine compared to the licensed Meningococcal polysaccharide groups A, C, W-135 and Y (Nimenrix®) Conjugate vaccine in toddlers 12 to 23 months of age in the European Union (EU). The toddlers were either meningococcal vaccine naïve or had received monovalent meningococcal C (MenC) vaccination during infancy to evaluate any potential impact of the meningococcal vaccine background on the immunogenicity and safety profile of the investigational product.

Primary Objectives:

• To demonstrate the non-inferiority of the antibody response to meningococcal serogroups A, C, Y, and W after a single dose of MenACYW Conjugate vaccine or Nimenrix® in toddlers who either were meningococcal vaccine naïve or had received monovalent MenC vaccination during infancy.

• To demonstrate the non-inferiority of the antibody response to meningococcal serogroups A, C, Y, and W after a single dose of MenACYW Conjugate vaccine or Nimenrix® in meningococcal vaccine naïve toddlers.

Secondary Objectives:

• To compare the antibody responses (geometric mean titers [GMTs]) to meningococcal serogroups A, C, Y, and W after a dose of MenACYW Conjugate vaccine or Nimenrix® as measured by serum bactericidal assay using human complement (hSBA) in toddlers who either were meningococcal vaccine naïve or had received monovalent MenC vaccination during infancy.

• To compare the antibody responses (GMTs) to meningococcal serogroups A, C, Y, and W after a dose of MenACYW Conjugate vaccine or Nimenrix® as measured by hSBA in meningococcal vaccine naïve toddlers.

• To compare the antibody responses (GMTs) to meningococcal serogroups A, C, Y, and W after a dose of MenACYW Conjugate vaccine or Nimenrix® as measured by hSBA in toddlers who received monovalent MenC vaccination during infancy.

Condition or Disease	Intervention/Treatment	Phase
Meningitis; Meningococcal Meningitis; Meningococcal Infections	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; Biological: Meningococcal polysaccharide groups A, C, W-135 and Y Conjugate vaccine; Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; Biological: Meningococcal polysaccharide groups A, C, W-135 and Y Conjugate vaccine	Phase 3

Detailed Description

Healthy toddlers were randomized depending on their meningococcal priming vaccination background (either meningococcal vaccine naïve or primed with MenC) and received a single dose of either MenACYW Conjugate vaccine or Nimenrix®. They were assessed for immunogenicity at baseline (pre-vaccination) and 30 to 44 days post-vaccination. Safety information were collected post-vaccination and throughout the entire study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 918 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Toddlers 12 to 23 Months of Age.
• Actual Study Start Date: Feb 24, 2017
• Actual Primary Completion Date: Oct 26, 2017
• Actual Study Completion Date: Oct 26, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1(Meningococcal Vaccine-Naive):MenACYW Conjugate Vaccine Healthy, meningococcal vaccine naive toddlers aged 12 to 23 months received a single dose of MenACYW Conjugate vaccine on Day 0.	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular; Other Names: MenACYW Conjugate vaccine
Experimental: Group 2 (Meningococcal Vaccine-Naive): Nimenrix® Healthy, meningococcal vaccine naive toddlers aged 12 to 23 months received a single dose of Nimenrix® vaccine on Day 0.	Biological: Meningococcal polysaccharide groups A, C, W-135 and Y Conjugate vaccine; 0.5 mL, Intramuscular; Other Names: Nimenrix®
Experimental: Group 3 (MenC-Primed): MenACYW Conjugate Vaccine Healthy, meningococcal C vaccine primed toddlers aged 12 to 23 months received a single dose of MenACYW Conjugate vaccine on Day 0.	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 mL, Intramuscular; Other Names: MenACYW Conjugate vaccine
Experimental: Group 4 (MenC-Primed): Nimenrix® Healthy, meningococcal C vaccine primed toddlers aged 12 to 23 months received a single dose of Nimenrix® vaccine on Day 0.	Biological: Meningococcal polysaccharide groups A, C, W-135 and Y Conjugate vaccine; 0.5 mL, Intramuscular; Other Names: Nimenrix®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Antibody Titers Greater Than or Equal to (>=) 1:8 Against Meningococcal Serogroups A, C, Y, and W in Toddlers Who Either Were Meningococcal Vaccine Naïve or Had Received Monovalent MenC Vaccination During Infancy [Day 30 (post-vaccination)]

   Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by serum bactericidal assay using human complement (hSBA). Data for this outcome measure were planned to be analyzed for the pooled population of MenACYW Conjugate vaccine and Nimenrix® reporting groups.

2. Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® in Meningococcal Vaccine Naïve Toddlers [Day 30 (post-vaccination)]

   Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by hSBA.

Secondary Outcome Measures

1. Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W in Toddlers Who Either Were Meningococcal Vaccine Naïve or Had Received Monovalent MenC Vaccination During Infancy [Day 30 (post-vaccination)]

   Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by hSBA.

2. Geometric Mean Titers of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® in Vaccine Naive Toddlers [Day 30 (post-vaccination)]

   Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by hSBA.

3. Geometric Mean Titers of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® in Toddlers Who Had Received Monovalent MenC Vaccination During Infancy [Day 30 (post-vaccination)]

   Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by hSBA.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Months to 23 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Aged 12 to 23 months on the day of the first study visit.

• Participants had received all recommended standard-of-care non-meningococcal vaccinations according to his/her age as per local regulations.

• Informed consent form (ICF) had been signed and dated by the parent/legally acceptable representative.

• Participant and parent/legally acceptable representative were able to attend all scheduled visits and complied with all trial procedures.

• Covered by health insurance if required by local regulations.

• Participants had received any meningococcal vaccine in the second year of life (i.e., from 12 months of age).

• For Inclusion in Groups 1 and 2: Participants must not had received any vaccination against meningococcal disease with either a trial vaccine or a licensed meningococcal vaccine (i.e., polyvalent, polysaccharide, or Conjugate meningococcal vaccine containing serogroups A, C, W, Y, B; or any monovalent or bivalent meningococcal vaccine).

• For Inclusion in Groups 3 and 4: Participants must had previously received at least 1 dose of licensed monovalent meningococcal C Conjugate (MenC) vaccine during infancy (i.e., before 12 months of age).

Exclusion Criteria:

• Participation in the 4 weeks preceding the trial vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.

• Receipt of any vaccine in the 4 weeks (28 days) preceding the trial vaccination or planned receipt of any vaccine prior to Visit 2 except for influenza vaccination, which may be received at least 2 weeks before or after study investigational vaccines. This exception included monovalent pandemic influenza vaccines and multivalent influenza vaccines.

• Receipt of immune globulins, blood or blood-derived products in the past 3 months.

• For Groups 1 and 2 only: Vaccination against meningococcal disease with either a trial vaccine or a licensed meningococcal vaccine (i.e., polyvalent, polysaccharide, or Conjugate meningococcal vaccine containing serogroups A, C, W, Y, B; or any monovalent or bivalent meningococcal vaccine).

• For Groups 3 and 4 only: Vaccination against meningococcal disease with either a trial vaccine or a licensed meningococcal vaccine (i.e., polyvalent, polysaccharide, or Conjugate meningococcal vaccine containing serogroups A, C, W, Y, B; or any monovalent B meningococcal vaccine), except licensed monovalent meningococcal C Conjugate (MenC) vaccination received during infancy.

• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).

• History of meningococcal infection, confirmed either clinically, serologically, or microbiologically.

• At high risk for meningococcal infection during the trial (specifically, but not limited to, participants with persistent complement deficiency, with anatomic or functional asplenia, or participants travelling to countries with high endemic or epidemic disease).

• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances.

• Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine.

• Personal history of Guillain-Barré Syndrome.

• Verbal report of thrombocytopenia, as reported by the parent/legally acceptable representative contraindicating intramuscular vaccination in the Investigator's opinion.

• Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the Investigator's opinion.

• Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion.

• Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.

• Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw - Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site 309	Espoo		Finland	02230
2	Investigational Site 301	Helsinki		Finland	00100
3	Investigational Site 306	Helsinki		Finland	00930
4	Investigational Site 302	Järvenpää		Finland	04400
5	Investigational Site 304	Kokkola		Finland	67100
6	Investigational Site 307	Oulu		Finland	90220
7	Investigational Site 303	Pori		Finland	28100
8	Investigational Site 305	Seinäjoki		Finland	60100
9	Investigational Site 308	Tampere		Finland	33100
10	Investigational Site 310	Turku		Finland	20520
11	Investigator Site 412	Aschaffenburg		Germany	63739
12	Investigator Site 401	Bramsche		Germany	49565
13	Investigator Site 407	Bretten		Germany	75015
14	Investigator Site 411	Bönnigheim		Germany	74357
15	Investigator Site 413	Datteln		Germany	45711
16	Investigator Site 408	Goch		Germany	47574
17	Investigator Site 406	Hamburg		Germany	22415
18	Investigator Site 415	Hamburg		Germany	22415
19	Investigator Site 404	Ludwigsfelde		Germany	14974
20	Investigator Site 409	Rosenheim		Germany	83026
21	Investigator Site 402	Tauberbischofsheim		Germany	97941
22	Investigator Site 403	Tauberbischofsheim		Germany	97941
23	Investigational Site 102	Budapest		Hungary	H 1042
24	Investigational Site 101	Budapest		Hungary	H 1188
25	Investigational Site 104	Győr		Hungary	H 9024
26	Investigational Site 105	Miskolc		Hungary	H 3527
27	Investigational Site 103	Szeged		Hungary	H 6723
28	Investigational Site 106	Székesfehérvár		Hungary	H 8000
29	Investigator Site 203	Barcelona		Spain	08950
30	Investigator Site 204	Galicia		Spain	15706
31	Investigator Site 205	Madrid		Spain	28007
32	Investigator Site 202	Madrid		Spain	28046
33	Investigator Site 201	Sevilla		Spain	41014

Sponsors and Collaborators

• Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director, Sanofi Pasteur SA

Study Documents (Full-Text)

• Study Protocol - Jul 20, 2016
• Statistical Analysis Plan - Apr 13, 2018

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT02955797
• Other Study ID Numbers: MET51; U1111-1161-2935; 2016-000749-30
• First Posted: Nov 4, 2016
• Last Update Posted: Apr 5, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Sanofi Pasteur, a Sanofi Company: Meningitis; Meningococcal Meningitis; MenACYW Conjugate vaccine; Nimenrix®; Menjugate®
• Additional relevant MeSH terms: Meningococcal Infections; Meningitis, Meningococcal; Meningitis; Vaccines

Study Results

Participant Flow

Recruitment Details	Study participants were enrolled in 34 centers in Spain, Hungary, Germany and Finland from 24 February 2017 to 21 September 2017.
Pre-assignment Detail	A total of 918 participants were enrolled and randomized in the study.

Arm/Group Title	Group 1(Meningococcal Vaccine-Naive):MenACYW Conjugate Vaccine	Group 2 (Meningococcal Vaccine-Naive): Nimenrix®	Group 3 (MenC-Primed) MenACYW Conjugate Vaccine	Group 4 (MenC-Primed): Nimenrix®
Arm/Group Description	Healthy, meningococcal vaccine naive toddlers aged 12 to 23 months received a single dose of Meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine on Day 0.	Healthy, meningococcal vaccine naive toddlers aged 12 to 23 months received a single dose of Meningococcal polysaccharide groups A, C, W-135 and Y (Nimenrix®) Conjugate vaccine on Day 0.	Healthy, meningococcal C (MenC) vaccine primed toddlers aged 12 to 23 months received a single dose of MenACYW Conjugate vaccine on Day 0.	Healthy, meningococcal C vaccine primed toddlers aged 12 to 23 months received a single dose of Nimenrix® vaccine on Day 0.
Period Title: Overall Study
STARTED	306	306	203	103
Safety Analysis Set (SafAS)	303	306	203	102
Per Protocol Analysis Set (PPAS)	293	296	198	99
COMPLETED	303	303	203	101
NOT COMPLETED	3	3	0	2

Baseline Characteristics

Arm/Group Title	Group 1(Meningococcal Vaccine-Naive):MenACYW Conjugate Vaccine	Group 2 (Meningococcal Vaccine-Naive): Nimenrix®	Group 3 (MenC-Primed): MenACYW Conjugate Vaccine	Group 4 (MenC-Primed): Nimenrix®	Total
Arm/Group Description	Healthy, meningococcal vaccine naive toddlers aged 12 to 23 months received a single dose of MenACYW Conjugate vaccine on Day 0.	Healthy, meningococcal vaccine naive toddlers aged 12 to 23 months received a single dose of Nimenrix® vaccine on Day 0.	Healthy, meningococcal C vaccine primed toddlers aged 12 to 23 months received a single dose of MenACYW Conjugate vaccine on Day 0.	Healthy, meningococcal C vaccine primed toddlers aged 12 to 23 months received a single dose of Nimenrix® vaccine on Day 0.	Total of all reporting groups
Overall Participants	306	306	203	103	918
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	16.1 (3.32)	16.2 (3.19)	14.0 (3.01)	13.8 (2.72)	15.4 (3.31)
Sex: Female, Male (Count of Participants)
Female	140 45.8%	145 47.4%	97 47.8%	53 51.5%	435 47.4%
Male	166 54.2%	161 52.6%	106 52.2%	50 48.5%	483 52.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 0.5%	0 0%	1 0.1%
Asian	1 0.3%	1 0.3%	0 0%	1 1%	3 0.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	2 0.7%	0 0%	1 1%	3 0.3%
White	115 37.6%	132 43.1%	197 97%	99 96.1%	543 59.2%
More than one race	2 0.7%	3 1%	5 2.5%	2 1.9%	12 1.3%
Unknown or Not Reported	188 61.4%	168 54.9%	0 0%	0 0%	356 38.8%
Region of Enrollment (Count of Participants)
Hungary	0 0%	0 0%	95 46.8%	50 48.5%	145 15.8%
Finland	188 61.4%	168 54.9%	0 0%	0 0%	356 38.8%
Germany	118 38.6%	138 45.1%	0 0%	0 0%	256 27.9%
Spain	0 0%	0 0%	108 53.2%	53 51.5%	161 17.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Antibody Titers Greater Than or Equal to (>=) 1:8 Against Meningococcal Serogroups A, C, Y, and W in Toddlers Who Either Were Meningococcal Vaccine Naïve or Had Received Monovalent MenC Vaccination During Infancy
Description	Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by serum bactericidal assay using human complement (hSBA). Data for this outcome measure were planned to be analyzed for the pooled population of MenACYW Conjugate vaccine and Nimenrix® reporting groups.
Time Frame	Day 30 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Per-protocol analysis set (PPAS) defined for accessing ACYW immune response data for participants who received at least one dose of study vaccine and had a valid post-vaccination serology result. Participants with pre-defined protocol deviations were excluded. Here, "Number analyzed" = participants with available data for each specified category.

Arm/Group Title	MenACYW Conjugate Vaccine (Groups 1 and 3)	Nimenrix® (Groups 2 and 4)
Arm/Group Description	All healthy meningococcal-vaccine naive and meningococcal C vaccine primed toddlers aged 12 to 23 months who received a single dose of MenACYW Conjugate vaccine on Day 0.	All meningococcal-vaccine naive and meningococcal C vaccine primed participants who a single dose of Nimenrix® vaccine on Day 0.
Measure Participants	491	395
Serogroup A	90.4 29.5%	91.6 29.9%
Serogroup C	99.2 32.4%	85.5 27.9%
Serogroup Y	94.3 30.8%	91.6 29.9%
Serogroup W	84.9 27.7%	84.0 27.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup A
	Type of Statistical Test	Non-Inferiority
	Comments	95% confidence interval (CI) was stratified on the priming status (meningococcal vaccine naïve or primed monovalent MenC vaccination during infancy) and calculated using the Wald method (normal approximation). Weighted average of the difference over strata was calculated using the Minimal Risk weights with the null variance method. Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI of the difference between the 2 percentages was greater than (>) -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	-2.03
	Confidence Interval	(2-Sided) 95%; -5.84 to 1.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup C
	Type of Statistical Test	Non-Inferiority
	Comments	95% CI was stratified on the priming status (meningococcal vaccine naïve or primed monovalent MenC vaccination during infancy) and calculated using the Wald method (normal approximation). Weighted average of the difference over strata was calculated using the Minimal Risk weights with the null variance method. Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI of the difference between the 2 percentages was > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	12.1
	Confidence Interval	(2-Sided) 95%; 8.16 to 16.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup Y
	Type of Statistical Test	Non-Inferiority
	Comments	95% CI was stratified on the priming status (meningococcal vaccine naïve or primed monovalent MenC vaccination during infancy) and calculated using the Wald method (normal approximation). Weighted average of the difference over strata was calculated using the Minimal Risk weights with the null variance method. Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI of the difference between the 2 percentages was > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	2.42
	Confidence Interval	(2-Sided) 95%; -1.34 to 6.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup W
	Type of Statistical Test	Non-Inferiority
	Comments	95% CI was stratified on the priming status (meningococcal vaccine naïve or primed monovalent MenC vaccination during infancy) and calculated using the Wald method (normal approximation). Weighted average of the difference over strata was calculated using the Minimal Risk weights with the null variance method. Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI of the difference between the 2 percentages was > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	0.458
	Confidence Interval	(2-Sided) 95%; -4.37 to 5.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® in Meningococcal Vaccine Naïve Toddlers
Description	Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by hSBA.
Time Frame	Day 30 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on PPAS. Here, "Number analyzed" = participants with available data for each specified category. Data for this outcome measure were not planned to be collected and analyzed for MenC-primed reporting groups (Groups 3 and 4).

Arm/Group Title	Group 1(Meningococcal Vaccine-Naive):MenACYW Conjugate Vaccine	Group 2 (Meningococcal Vaccine-Naive): Nimenrix®
Arm/Group Description	Healthy, meningococcal vaccine naive toddlers aged 12 to 23 months received a single dose of MenACYW Conjugate vaccine on Day 0.	Healthy, meningococcal vaccine naive toddlers aged 12 to 23 months received a single dose of Nimenrix® vaccine on Day 0.
Measure Participants	293	296
Serogroup A	90.8 29.7%	89.5 29.2%
Serogroup C	99.3 32.5%	81.4 26.6%
Serogroup Y	93.2 30.5%	91.6 29.9%
Serogroup W	83.6 27.3%	83.4 27.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup A
	Type of Statistical Test	Non-Inferiority
	Comments	95% CI of the difference in percentages was computed using the Wilson Score method without continuity correction. Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI of the difference between the 2 percentages was > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -3.6 to 6.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup C
	Type of Statistical Test	Non-Inferiority
	Comments	95% CI of the difference in percentages was computed using the Wilson Score method without continuity correction. Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI of the difference between the 2 percentages was > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	18
	Confidence Interval	(2-Sided) 95%; 13.6 to 22.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup Y
	Type of Statistical Test	Non-Inferiority
	Comments	95% CI of the difference in percentages was computed using the Wilson Score method without continuity correction. Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI of the difference between the 2 percentages was > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -2.76 to 6.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup W
	Type of Statistical Test	Non-Inferiority
	Comments	95% CI of the difference in percentages was computed using the Wilson Score method without continuity correction. Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI of the difference between the 2 percentages was > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -5.85 to 6.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W in Toddlers Who Either Were Meningococcal Vaccine Naïve or Had Received Monovalent MenC Vaccination During Infancy
Description	Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by hSBA.
Time Frame	Day 30 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on PPAS. Here, "Number analyzed" = participants with available data for each specified category. Data for this outcome measure were planned to be analyzed for the pooled population of MenACYW Conjugate vaccine and Nimenrix® reporting groups.

Arm/Group Title	MenACYW Conjugate Vaccine (Groups 1 and 3)	Nimenrix® (Groups 2 and 4)
Arm/Group Description	All healthy meningococcal-vaccine naive and meningococcal C vaccine primed toddlers aged 12 to 23 months who received a single dose of MenACYW Conjugate vaccine on Day 0.	All meningococcal vaccine naive and meningococcal C vaccine primed participants who a single dose of Nimenrix® vaccine on Day 0.
Measure Participants	491	395
Serogroup A	29.9	34.5
Serogroup C	880	77.1
Serogroup Y	41.7	31.9
Serogroup W	24.4	17.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup A
	Type of Statistical Test	Other
	Comments	95% CI of the ratio of post-vaccination GMTs was stratified on the priming vaccination status (meningococcal vaccine naïve or primed monovalent MenC vaccination) and calculated using an analysis of variance (ANOVA) model of log10-transformed titers.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.819
	Confidence Interval	(2-Sided) 95%; 0.697 to 0.963
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup C
	Type of Statistical Test	Other
	Comments	95% CI of the ratio of post-vaccination GMTs was stratified on the priming vaccination status (meningococcal vaccine naïve or primed monovalent MenC vaccination) and calculated using an ANOVA model of log10-transformed titers.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	7.59
	Confidence Interval	(2-Sided) 95%; 6.05 to 9.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup Y
	Type of Statistical Test	Other
	Comments	95% CI of the ratio of post-vaccination GMTs was stratified on the priming vaccination status (meningococcal vaccine naïve or primed monovalent MenC vaccination) and calculated using an ANOVA model of log10-transformed titers.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.28
	Confidence Interval	(2-Sided) 95%; 1.09 to 1.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup W
	Type of Statistical Test	Other
	Comments	95% CI of the ratio of post-vaccination GMTs was stratified on the priming vaccination status (meningococcal vaccine naïve or primed monovalent MenC vaccination) and calculated using an ANOVA model of log10-transformed titers.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 1.12 to 1.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Geometric Mean Titers of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® in Vaccine Naive Toddlers
Description	Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by hSBA.
Time Frame	Day 30 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on PPAS. Here, "Number analyzed" = participants with available data for each specified category.

Arm/Group Title	Group 1(Meningococcal Vaccine-Naive):MenACYW Conjugate Vaccine	Group 2 (Meningococcal Vaccine-Naive): Nimenrix®
Arm/Group Description	Healthy, meningococcal vaccine naive toddlers aged 12 to 23 months received a single dose of MenACYW Conjugate vaccine on Day 0.	Healthy, meningococcal vaccine naive toddlers aged 12 to 23 months received a single dose of Nimenrix® vaccine on Day 0.
Measure Participants	293	296
Serogroup A	28.7	28.0
Serogroup C	436	26.4
Serogroup Y	38.0	32.2
Serogroup W	22.0	16.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup A
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup C
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	16.5
	Confidence Interval	(2-Sided) 95%; 13.4 to 20.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup Y
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup W
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.34
	Confidence Interval	(2-Sided) 95%; 1.1 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Geometric Mean Titers of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® in Toddlers Who Had Received Monovalent MenC Vaccination During Infancy
Description	Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by hSBA.
Time Frame	Day 30 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on PPAS. Here, "Number analyzed" = participants with available data for each specified category.

Arm/Group Title	Group 3 (MenC-Primed): MenACYW Conjugate Vaccine	Group 4 (MenC-Primed): Nimenrix®
Arm/Group Description	Healthy, meningococcal C vaccine primed toddlers aged 12 to 23 months received a single dose of MenACYW Conjugate vaccine on Day 0.	Healthy, meningococcal C vaccine primed toddlers aged 12 to 23 months received a single dose of Nimenrix® vaccine on Day 0.
Measure Participants	198	99
Serogroup A	31.8	64.0
Serogroup C	2514	1883
Serogroup Y	48.0	31.3
Serogroup W	28.7	22.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup A
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	0.496
	Confidence Interval	(2-Sided) 95%; 0.367 to 0.672
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup C
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.34
	Confidence Interval	(2-Sided) 95%; 0.814 to 2.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup Y
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.53
	Confidence Interval	(2-Sided) 95%; 1.15 to 2.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MenACYW Conjugate Vaccine (Groups 1 and 3), Nimenrix® (Groups 2 and 4)
	Comments	Serogroup W
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95%; 0.944 to 1.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse event (AE) data were collected from Day 0 (post-vaccination) up to 30 days after vaccination. Solicited Reactions (SRs) data were collected within 7 days after vaccination. Serious adverse events (SAEs) data were collected throughout the study (up to 30 days after vaccination).
Adverse Event Reporting Description	Analysis was performed on 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.
Arm/Group Title	Group 1(Meningococcal Vaccine-Naive):MenACYW Conjugate Vaccine		Group 2 (Meningococcal Vaccine-Naive): Nimenrix®		Group 3 (MenC-Primed): MenACYW Conjugate Vaccine		Group 4 (MenC-Primed): Nimenrix®
Arm/Group Description	Healthy, meningococcal vaccine naive toddlers aged 12 to 23 months received a single dose of MenACYW Conjugate vaccine on Day 0.		Healthy, meningococcal vaccine naive toddlers aged 12 to 23 months received a single dose of Nimenrix® vaccine on Day 0.		Healthy, meningococcal C vaccine primed toddlers aged 12 to 23 months received a single dose of MenACYW Conjugate vaccine on Day 0.		Healthy, meningococcal C vaccine primed toddlers aged 12 to 23 months received a single dose of Nimenrix® vaccine on Day 0.
All Cause Mortality
	Group 1(Meningococcal Vaccine-Naive):MenACYW Conjugate Vaccine		Group 2 (Meningococcal Vaccine-Naive): Nimenrix®		Group 3 (MenC-Primed): MenACYW Conjugate Vaccine		Group 4 (MenC-Primed): Nimenrix®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/303 (0%)		0/306 (0%)		0/203 (0%)		0/102 (0%)
Serious Adverse Events
	Group 1(Meningococcal Vaccine-Naive):MenACYW Conjugate Vaccine		Group 2 (Meningococcal Vaccine-Naive): Nimenrix®		Group 3 (MenC-Primed): MenACYW Conjugate Vaccine		Group 4 (MenC-Primed): Nimenrix®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/303 (0.7%)		1/306 (0.3%)		2/203 (1%)		2/102 (2%)
Blood and lymphatic system disorders
Haemolytic Uraemic Syndrome	1/303 (0.3%)	1	0/306 (0%)	0	0/203 (0%)	0	0/102 (0%)	0
Congenital, familial and genetic disorders
Intestinal Malrotation	1/303 (0.3%)	1	0/306 (0%)	0	0/203 (0%)	0	0/102 (0%)	0
Infections and infestations
Bronchitis	0/303 (0%)	0	0/306 (0%)	0	0/203 (0%)	0	1/102 (1%)	1
Campylobacter Gastroenteritis	0/303 (0%)	0	0/306 (0%)	0	1/203 (0.5%)	1	0/102 (0%)	0
Gastroenteritis Escherichia Coli	1/303 (0.3%)	1	0/306 (0%)	0	0/203 (0%)	0	0/102 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/303 (0%)	0	1/306 (0.3%)	1	0/203 (0%)	0	0/102 (0%)	0
Craniocerebral Injury	0/303 (0%)	0	0/306 (0%)	0	1/203 (0.5%)	1	0/102 (0%)	0
Investigations
Blood Immunoglobulin A Decreased	0/303 (0%)	0	0/306 (0%)	0	0/203 (0%)	0	1/102 (1%)	1
Nervous system disorders
Febrile Convulsion	1/303 (0.3%)	1	0/306 (0%)	0	0/203 (0%)	0	0/102 (0%)	0
Seizure	0/303 (0%)	0	0/306 (0%)	0	1/203 (0.5%)	1	0/102 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchospasm	0/303 (0%)	0	0/306 (0%)	0	0/203 (0%)	0	1/102 (1%)	1
Other (Not Including Serious) Adverse Events
	Group 1(Meningococcal Vaccine-Naive):MenACYW Conjugate Vaccine		Group 2 (Meningococcal Vaccine-Naive): Nimenrix®		Group 3 (MenC-Primed): MenACYW Conjugate Vaccine		Group 4 (MenC-Primed): Nimenrix®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	261/303 (86.1%)		266/306 (86.9%)		151/203 (74.4%)		65/102 (63.7%)
Gastrointestinal disorders
Diarrhoea	23/303 (7.6%)	23	16/306 (5.2%)	16	8/203 (3.9%)	8	4/102 (3.9%)	4
Teething	16/303 (5.3%)	18	13/306 (4.2%)	19	12/203 (5.9%)	15	6/102 (5.9%)	7
Vomiting	23/303 (7.6%)	24	13/306 (4.2%)	13	21/203 (10.3%)	21	8/102 (7.8%)	8
General disorders
Crying	106/303 (35%)	109	111/306 (36.3%)	112	48/203 (23.6%)	48	23/102 (22.5%)	23
Injection Site Erythema	122/303 (40.3%)	123	116/306 (37.9%)	116	52/203 (25.6%)	52	21/102 (20.6%)	21
Injection Site Pain	122/303 (40.3%)	122	113/306 (36.9%)	113	55/203 (27.1%)	55	20/102 (19.6%)	21
Injection Site Swelling	63/303 (20.8%)	63	52/306 (17%)	52	35/203 (17.2%)	35	9/102 (8.8%)	9
Pyrexia	40/303 (13.2%)	42	48/306 (15.7%)	48	29/203 (14.3%)	29	14/102 (13.7%)	15
Infections and infestations
Bronchitis	3/303 (1%)	4	2/306 (0.7%)	2	11/203 (5.4%)	11	1/102 (1%)	1
Nasopharyngitis	15/303 (5%)	19	18/306 (5.9%)	18	2/203 (1%)	2	0/102 (0%)	0
Rhinitis	21/303 (6.9%)	22	25/306 (8.2%)	27	5/203 (2.5%)	5	0/102 (0%)	0
Upper Respiratory Tract Infection	49/303 (16.2%)	55	39/306 (12.7%)	43	14/203 (6.9%)	14	7/102 (6.9%)	8
Metabolism and nutrition disorders
Decreased Appetite	91/303 (30%)	93	94/306 (30.7%)	94	56/203 (27.6%)	56	28/102 (27.5%)	28
Nervous system disorders
Somnolence	64/303 (21.1%)	64	55/306 (18%)	55	51/203 (25.1%)	51	19/102 (18.6%)	19
Psychiatric disorders
Irritability	144/303 (47.5%)	145	127/306 (41.5%)	128	76/203 (37.4%)	76	36/102 (35.3%)	36
Respiratory, thoracic and mediastinal disorders
Cough	11/303 (3.6%)	11	13/306 (4.2%)	16	13/203 (6.4%)	13	5/102 (4.9%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable participant matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.