Safety and Immunogenicity of 2 or 3 Doses of MenACWY Conjugate Vaccine in Healthy Infants and the Effects of a Booster Dose of MenACWY Administered in the Second Year of Life

• Sponsor: Novartis Vaccines (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01214837
• Collaborator: (none)
• Enrollment: 751
• Locations: 40
• Arms: 3
• Duration (Months): 19
• Patients Per Site: 18.8
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study was to assess immunogenicity of a 3-dose versus 4-dose infant vaccination schedule including kinetics of immune response in the early phases of the series.

Condition or Disease	Intervention/Treatment	Phase
Meningococcal Disease; Meningococcal Meningitis	Biological: MenACWY-CRM; Biological: MenACWY-CRM; Biological: Routine Vaccines	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 751 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase 3b, Randomized, Open-Label, Multi-Center Study to Evaluate the Safety and Immunogenicity of 2 or 3 Doses of MenACWY Conjugate Vaccine in Healthy Infants and the Effects of a Booster Dose of MenACWY Administered in the Second Year of Life.
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MenACWY3 Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	Biological: MenACWY-CRM; This group received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.; Biological: Routine Vaccines; Each 0.5 mL dose of the pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein) is formulated to contain approximately 2.2 μg of each of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F saccharides.
Experimental: MenACWY4 All the subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.	Biological: MenACWY-CRM; This group received a 3-dose primary series at 2, 4, and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.; Biological: Routine Vaccines; Each 0.5 mL dose of the pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein) is formulated to contain approximately 2.2 μg of each of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F saccharides.
Placebo Comparator: Routine Vaccines Subjects received routine vaccines only, including PCV-13, at 2, 4 and 6 months of age and a toddler dose at 12 months of age.	Biological: Routine Vaccines; Each 0.5 mL dose of the pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein) is formulated to contain approximately 2.2 μg of each of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F saccharides.

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With Serum Bactericidal Activity Using Human Complement (hSBA) ≥ 1:8 Against N. Meningitidis Serogroups A, C, W and Y Following a 4-dose Schedule of Men ACWY Vaccination. [13 months of age]

   The immune response was assessed in terms of percentage of subjects with hSBA ≥ 1:8 against N. meningitidis serogroups A, C, W and Y following 4 doses of Men ACWY vaccine given to infants at 2, 4, 6 and 12 months of age.

2. Percentage of Subjects With hSBA ≥ 1:8 Against N. Meningitidis Serogroups A, C, W and Y Following 4-Dose and 3-Dose Schedule of Men ACWY Vaccination. [13 months of age]

   The immune response was assessed in terms of percentage of subjects with hSBA ≥ 1:8 against N. meningitidis serogroups A, C, W and Y following 4 doses of Men ACWY vaccine given to infants at 2, 4,6 and 12 months of age and 3 doses of Men ACWY given to infants at 2, 4 and 12 months of age.

Secondary Outcome Measures

1. Percentage of Subjects With hSBA ≥1:8 Against N. Meningitidis Serogroups A, C, W and Y at Baseline (2 Months of Age) and at 3, 4, 5, and 7 Months of Age. [Baseline (2 months of age), 3 months, 4 months , 5 months and 7 months of age]

   Antibody levels were assessed in terms of percentage of subjects with hSBA ≥ 1:8 against N. meningitidis serogroups A, C, W and Y at baseline (2 months of age) and at 3, 4, 5 and 7 months of age.

2. Geometric Mean hSBA Titers Against N Meningitis Serogroups A, C, W and Y at Baseline (2 Months of Age) and at 3, 4, 5, and 7 Months of Age. [Baseline(2 months of age), 3 months, 4 months , 5 months and 7 months of age.]

   Antibody levels were assessed in terms of geometric mean titers (GMTs) against N. meningitidis serogroups A, C, W and Y at baseline (2 Months of Age) and at 3, 4, 5, and 7 Months of Age.

3. Percentage of Subjects With hSBA ≥1:8 Following 2 and 3 Infant Doses of MenACWY. [12 months of age.]

   Percentage of subjects with hSBA ≥1:8 against N meningitis serogroups A, C, W and Y was assessed following 2 and 3 infant doses of MenACWY as measured prior to the toddler dose at 12 months of age.

4. Geometric Mean hSBA Titers Following 2 and 3 Infant Doses of MenACWY. [12 months of age]

   The immune response was assessed in terms of GMTs against N. meningitidis serogroups A, C, W and Y following 2 and 3 infant doses of MenACWY as measured prior to the toddler dose at 12 months of age.

5. GMTs at 13 Months of Age After Completion of 3- and 4-Dose Series of MenACWY. [13 months of age]

   Immune response was assessed in terms of GMTs against N meningitis serogroups A, C, W and Y at 1 month after completion of a 3- and 4- dose series of MenACWY.

6. Percentage of Subjects With 4-fold Increase in hSBA Titers Against N Meningitis Serogroups A, C, W and Y Between 12 and 13 Months of Age. [13 months of age]

   The immune response was assessed in terms of percentage of subjects with 4-fold increase in hSBA titers between post and pre toddler dose against N meningitis serogroups A, C, W and Y, 1 month after completing a 3- or 4-dose series of MenACWY.

7. Effect of Concomitant Administration of 2 or 3 Doses of MenACWY on Immune Response to PCV-13 Antigens at 7 Months of Age. [7 months of age.]

   Percentage of subjects with IgG concentration ≥ 0.35 μg/mL against pneumococcal conjugate vaccine (PCV-13) antigens at 7 Months of age following concomitant administration of 2 or 3 doses of MenACWY with PCV-13.

8. Effect of Concomitant Administration of 3 or 4 Doses of MenACWY on Immune Response to PCV-13 Antigens at 13 Months of Age. [13 months of age.]

   Geometric mean concentrations (GMCs) of antibodies against PCV-13 vaccine antigens at 13 months of age following concomitant administration of a 3- or 4-dose series of MenACWY with PCV-13.

9. Percentage Of Subjects Reporting at Least One Severe Systemic Solicited Adverse Event. [Within 7 days]

   Safety was assessed as the percentages of subjects who reported severe solicited systemic adverse events within 30 minutes through day 7 of MenACWY administration with concomitant vaccines vs. concomitant vaccines alone.

10. Number Of Subjects Reporting Solicited Local or Systemic Adverse Events. [Day 1 through Day 7]

    Safety was assessed as the number of subjects who reported solicited local or systemic adverse events between 6 hours and day 7 after administration of MenACWY with concomitant vaccines vs. concomitant vaccines alone.

11. Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination. [13 months of age]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Days to 89 Days
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Infants of both genders who are in generally good health will be eligible for this study. For infants to be enrolled, the parents/legal representatives need to provide written informed consent and to be available for all study visits.

Exclusion Criteria:

• Serious, acute, or chronic illnesses are reasons for exclusion.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Fayetteville	Arkansas	United States
3		Jonesboro	Arkansas	United States
4		Little Rock	Arkansas	United States
5		Fountain Valley	California	United States
6		Huntington Beach	California	United States
7		Madera	California	United States
8		Nampa	Idaho	United States
9	Cotton ONeil Clinical Research	Topeka	Kansas	United States	66604
10	Cotton ONeil Clinical Research	Topeka	Kansas	United States	66614
11		Bardstown	Kentucky	United States
12	Bluegrass Clinical Research (Bardstown Road)	Louisville	Kentucky	United States
13	Bluegrass Clinical Research (Brownsboro Park Blvd)	Louisville	Kentucky	United States
14		Springfield	Kentucky	United States
15		Haughton	Louisiana	United States
16		Shreveport	Louisiana	United States
17		Niles	Michigan	United States
18		Lincoln	Nebraska	United States
19	Children's Physicians Dundee	Omaha	Nebraska	United States
20	Creighton Univ	Omaha	Nebraska	United States
21		Binghamton	New York	United States
22		Johnson City	New York	United States
23		Syracuse	New York	United States
24		Dayton	Ohio	United States
25		Huber Heights	Ohio	United States
26		Kettering	Ohio	United States
27		Tulsa	Oklahoma	United States
28		Kingsport	Tennessee	United States
29		Lebanon	Tennessee	United States
30		San Antonio	Texas	United States
31		Tomball	Texas	United States
32		Layton	Utah	United States
33		Saint George	Utah	United States
34		Salt Lake City	Utah	United States
35		Richmond	Virginia	United States
36	Rockwood Clinic P S	Spokane	Washington	United States	99202
37	Rockwood Clinic P S	Spokane	Washington	United States	99218
38		Sudbury	Ontario	Canada
39		Toronto	Ontario	Canada
40		Pierrefonds	Quebec	Canada

Sponsors and Collaborators

• Novartis Vaccines

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Vaccines
• ClinicalTrials.gov Identifier: NCT01214837
• Other Study ID Numbers: V59_36
• First Posted: Oct 5, 2010
• Last Update Posted: Oct 9, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Novartis Vaccines: Meningococcal; ACWY; Conjugate Vaccine; Meningitis; Infants; Persistence
• Additional relevant MeSH terms: Meningococcal Infections; Meningitis, Meningococcal; Meningitis

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled at 3 sites in Canada and 37 sites in United States of America.
Pre-assignment Detail	All the enrolled subjects were included in the trial.

Arm/Group Title	MenACWY3	MenACWY4	Routine Vaccines
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	All subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.	Subjects received routine vaccines only, including pneumococcal 13-valent conjugate vaccine (PCV-13), at 2, 4, 6 and 12 months of age.
Period Title: Overall Study
STARTED	249	256	246
COMPLETED	195	192	184
NOT COMPLETED	54	64	62

Baseline Characteristics

Arm/Group Title	MenACWY3	MenACWY4	Routine Vaccines	Total
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	All subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.	Subjects received routine vaccines only, including PCV-13, at 2, 4, 6 and 12 months of age.	Total of all reporting groups
Overall Participants	249	256	246	751
Age (Days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Days]	66.4 (7.1)	66.7 (7.4)	66.7 (7.0)	66.6 (7.2)
Sex: Female, Male (Count of Participants)
Female	126 50.6%	123 48%	106 43.1%	355 47.3%
Male	123 49.4%	133 52%	140 56.9%	396 52.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With Serum Bactericidal Activity Using Human Complement (hSBA) ≥ 1:8 Against N. Meningitidis Serogroups A, C, W and Y Following a 4-dose Schedule of Men ACWY Vaccination.
Description	The immune response was assessed in terms of percentage of subjects with hSBA ≥ 1:8 against N. meningitidis serogroups A, C, W and Y following 4 doses of Men ACWY vaccine given to infants at 2, 4, 6 and 12 months of age.
Time Frame	13 months of age

Outcome Measure Data

Analysis Population Description

Analysis was done on the Toddler Per Protocol Population (PPS) - all subjects who received all doses of vaccine correctly, and provided evaluable serum samples at the relevant time points, and had no major protocol violation as defined prior to unblinding through 13 month timepoint.

Arm/Group Title	MenACWY4
Arm/Group Description	All subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.
Measure Participants	152
Serogroup A (N=141)	96
Serogroup C	99
Serogroup W (N=138)	99
Serogroup Y (N=146)	99

2. Primary Outcome

Title	Percentage of Subjects With hSBA ≥ 1:8 Against N. Meningitidis Serogroups A, C, W and Y Following 4-Dose and 3-Dose Schedule of Men ACWY Vaccination.
Description	The immune response was assessed in terms of percentage of subjects with hSBA ≥ 1:8 against N. meningitidis serogroups A, C, W and Y following 4 doses of Men ACWY vaccine given to infants at 2, 4,6 and 12 months of age and 3 doses of Men ACWY given to infants at 2, 4 and 12 months of age.
Time Frame	13 months of age

Outcome Measure Data

Analysis Population Description

Analysis was done on Toddler PPS.

Arm/Group Title	MenACWY3	MenACWY4
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	Subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.
Measure Participants	160	152
Serogroup A (N=146,141)	88	96
Serogroup C	95	99
Serogroup W (N=153,138)	99	99
Serogroup Y (N=154,146)	100	99

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, MenACWY4
	Comments	Non-inferiority of Men ACWY 3-dose series (doses at 2, 4 and 12 months) to 4-dose series (doses at 2, 4, 6 and 12 months of age) against serogroup A at 13 months of age.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the difference in percentage of subjects with hSBA titers ≥ 1:8 against N. meningitidis serogroups C, W and Y between the 3-dose series and (minus) the 4-dose series, is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	-7
	Confidence Interval	(2-Sided) 95%; -14 to -1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, MenACWY4
	Comments	Non-inferiority of Men ACWY 3-dose series (doses at 2, 4 and 12 months) to 4-dose series (doses at 2, 4, 6 and 12 months of age) against serogroup C at 13 months of age.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the difference in percentage of subjects with hSBA titers ≥ 1:8 against N. meningitidis serogroups C, W and Y between the 3-dose series and (minus) the 4-dose series, is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	-4
	Confidence Interval	(2-Sided) 95%; -8 to 0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, MenACWY4
	Comments	Non-inferiority of Men ACWY 3-dose series (doses at 2, 4 and 12 months) to 4-dose series (doses at 2, 4, 6 and 12 months of age) against serogroup W at 13 months of age.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the difference in percentage of subjects with hSBA titers ≥ 1:8 against N. meningitidis serogroups C, W and Y between the 3-dose series and (minus) the 4-dose series, is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; -3 to 3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, MenACWY4
	Comments	Non-inferiority of Men ACWY 3-dose series (doses at 2, 4 and 12 months) to 4-dose series (doses at 2, 4, 6 and 12 months of age) against serogroup Y at 13 months of age.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the difference in percentage of subjects with hSBA titers ≥ 1:8 against N. meningitidis serogroups C, W and Y between the 3-dose series and (minus) the 4-dose series, is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	1
	Confidence Interval	(2-Sided) 95%; -2 to 4
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Subjects With hSBA ≥1:8 Against N. Meningitidis Serogroups A, C, W and Y at Baseline (2 Months of Age) and at 3, 4, 5, and 7 Months of Age.
Description	Antibody levels were assessed in terms of percentage of subjects with hSBA ≥ 1:8 against N. meningitidis serogroups A, C, W and Y at baseline (2 months of age) and at 3, 4, 5 and 7 months of age.
Time Frame	Baseline (2 months of age), 3 months, 4 months , 5 months and 7 months of age

Outcome Measure Data

Analysis Population Description

Analysis was done on Infant PPS - all subjects who received all doses of vaccine correctly, and provided evaluable serum samples at the relevant time points, and had no major protocol violation as defined prior to unblinding, through the 7 month timepoint.

Arm/Group Title	MenACWY3	MenACWY4	Routine Vaccines
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	Subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.	Subjects received routine vaccines only, including PCV-13, at 2, 4, 6 and 12 months of age.
Measure Participants	185	176	187
Serogroup A (baseline; N=0,0,166)	NA	NA	4
Serogroup A (3 months; N=0,82,0)	NA	9	NA
Serogroup A (4 months; N=0,70,0)	NA	4	NA
Serogroup A (5 months; N=157,0,0)	43	NA	NA
Serogroup A (7 months; N=169,157,171)	23	84	1
Serogroup C (baseline; N=0,0,167)	NA	NA	9
Serogroup C (3 months; N=0,85,0)	NA	28	NA
Serogroup C (4 months; N=0,70,0)	NA	41	NA
Serogroup C (5 months; N=170,0,0)	86	NA	NA
Serogroup C (7 months)	71	95	1
Serogroup W (baseline; N=0,0,157)	NA	NA	20
Serogroup W (3 months; N=0,84,0)	NA	15	NA
Serogroup W (4 months; N=0,71,0)	NA	35	NA
Serogroup W (5 months; N=162,0,0)	86	NA	NA
Serogroup W (7 months; N=179,162,181)	74	99	1
Serogroup Y (baseline; N=0,0,150)	NA	NA	7
Serogroup Y (3 months; N=0,80,0)	NA	8	NA
Serogroup Y (4 months; N=0,69,0)	NA	7	NA
Serogroup Y (5 months; N=152,0,0)	67	NA	NA
Serogroup Y (7 months; N=170,163,173)	48	94	0

4. Secondary Outcome

Title	Geometric Mean hSBA Titers Against N Meningitis Serogroups A, C, W and Y at Baseline (2 Months of Age) and at 3, 4, 5, and 7 Months of Age.
Description	Antibody levels were assessed in terms of geometric mean titers (GMTs) against N. meningitidis serogroups A, C, W and Y at baseline (2 Months of Age) and at 3, 4, 5, and 7 Months of Age.
Time Frame	Baseline(2 months of age), 3 months, 4 months , 5 months and 7 months of age.

Outcome Measure Data

Analysis Population Description

Analysis was done on the Infant PPS.

Arm/Group Title	MenACWY3	MenACWY4	Routine Vaccines
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	Subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.	Subjects received routine vaccines only, including PCV-13, at 2, 4, 6 and 12 months of age.
Measure Participants	185	176	187
Serogroup A (baseline; N=0,0,166)	NA	NA	2.18
Serogroup A (3 months; N=0,82,0)	NA	2.63	NA
Serogroup A (4 months; N=0,70,0)	NA	2.18	NA
Serogroup A (5 months; N=157,0,0)	7.09	NA	NA
Serogroup A (7 months; N=169,157,171)	3.68	28	2.02
Serogroup C (baseline; N=0,0,167)	NA	NA	2.52
Serogroup C (3 months; N=0,85,0)	NA	4.79	NA
Serogroup C (4 months; N=0,70,0)	NA	6.44	NA
Serogroup C (5 months; N=170,0,0)	50	NA	NA
Serogroup C (7 months)	17	86	2.03
Serogroup W (baseline; N=0,0,157)	NA	NA	3.32
Serogroup W (3 months; N=0,84,0)	NA	3	NA
Serogroup W (4 months;N=0,71,0)	NA	4.38	NA
Serogroup W (5 months; N=162,0,0)	55	NA	NA
Serogroup W (7 months; N=179,162,181)	17	90	2.04
Serogroup Y (baseline; N=0,0,150)	NA	NA	2.47
Serogroup Y (3 months; N=0,80,0)	NA	2.5	NA
Serogroup Y (4 months; N=0,69,0)	NA	2.46	NA
Serogroup Y (5 months; N=152,0,0)	20	NA	NA
Serogroup Y (7 months; N=170,163,173)	7.56	52	2

5. Secondary Outcome

Title	Percentage of Subjects With hSBA ≥1:8 Following 2 and 3 Infant Doses of MenACWY.
Description	Percentage of subjects with hSBA ≥1:8 against N meningitis serogroups A, C, W and Y was assessed following 2 and 3 infant doses of MenACWY as measured prior to the toddler dose at 12 months of age.
Time Frame	12 months of age.

Outcome Measure Data

Analysis Population Description

Analysis was done on the Toddler PPS.

Arm/Group Title	MenACWY3	MenACWY4
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	Subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.
Measure Participants	149	147
Serogroup A (N=141,138)	6	22
Serogroup C	19	48
Serogroup W (N=149,142)	33	66
Serogroup Y (N=145,139)	25	55

6. Secondary Outcome

Title	Geometric Mean hSBA Titers Following 2 and 3 Infant Doses of MenACWY.
Description	The immune response was assessed in terms of GMTs against N. meningitidis serogroups A, C, W and Y following 2 and 3 infant doses of MenACWY as measured prior to the toddler dose at 12 months of age.
Time Frame	12 months of age

Outcome Measure Data

Analysis Population Description

Analysis was done on the Toddler PPS.

Arm/Group Title	MenACWY3	MenACWY4
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	Subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.
Measure Participants	149	147
Serogroup A (N=141,138)	2.28	3.65
Serogroup C	3.54	8.55
Serogroup W (N=149,142)	5.41	13
Serogroup Y (N=145,139)	3.82	9.65

7. Secondary Outcome

Title	GMTs at 13 Months of Age After Completion of 3- and 4-Dose Series of MenACWY.
Description	Immune response was assessed in terms of GMTs against N meningitis serogroups A, C, W and Y at 1 month after completion of a 3- and 4- dose series of MenACWY.
Time Frame	13 months of age

Outcome Measure Data

Analysis Population Description

Analysis was done on the Toddler PPS.

Arm/Group Title	MenACWY3	MenACWY4
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	Subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.
Measure Participants	160	152
Serogroup A (N=146,141)	59	94
Serogroup C	124	160
Serogroup W (N=153,138)	248	244
Serogroup Y (N=154,146)	212	254

8. Secondary Outcome

Title	Percentage of Subjects With 4-fold Increase in hSBA Titers Against N Meningitis Serogroups A, C, W and Y Between 12 and 13 Months of Age.
Description	The immune response was assessed in terms of percentage of subjects with 4-fold increase in hSBA titers between post and pre toddler dose against N meningitis serogroups A, C, W and Y, 1 month after completing a 3- or 4-dose series of MenACWY.
Time Frame	13 months of age

Outcome Measure Data

Analysis Population Description

Analysis was done on the Toddler PPS.

Arm/Group Title	MenACWY3	MenACWY4
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	Subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.
Measure Participants	147	147
Serogroup A (N=127,129)	88	95
Serogroup C	93	91
Serogroup W (N=140,131)	98	90
Serogroup Y (N=139,136)	100	96

9. Secondary Outcome

Title	Effect of Concomitant Administration of 2 or 3 Doses of MenACWY on Immune Response to PCV-13 Antigens at 7 Months of Age.
Description	Percentage of subjects with IgG concentration ≥ 0.35 μg/mL against pneumococcal conjugate vaccine (PCV-13) antigens at 7 Months of age following concomitant administration of 2 or 3 doses of MenACWY with PCV-13.
Time Frame	7 months of age.

Outcome Measure Data

Analysis Population Description

Analysis was done on the Infant PPS.

Arm/Group Title	MenACWY3	MenACWY4	Routine Vaccines
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	Subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.	Subjects received routine vaccines only, including PCV-13, at 2, 4, 6 and 12 months of age.
Measure Participants	160	137	158
1 (N=159,136,156)	93.7	100	94.2
3 (N=150,129,147)	79.3	87.6	82.3
4 (N=160,137,157)	94.4	97.1	96.8
5 (N=156,133,154)	84	93.2	88.3
6A (N=159,136,156)	98.1	99.3	98.1
6B (N=160,137,157)	84.4	94.9	84.7
7F (N=158,136,156)	100	100	99.4
9V (N=159,136,157)	89.3	96.3	92.4
14 (N=158,136,158)	99.4	100	97.5
18C (N=158,136,157)	97.5	97.8	100
19A (N=158,135,156)	95.6	92.6	98.1
19F (N=159,136,158)	100	100	99.4
23F (N=158,136,158)	93	95.6	91.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 2 doses of MenACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 1.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY3 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -6.1 to 5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 1.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY4 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	5.8
	Confidence Interval	(2-Sided) 95%; 3 to 10.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 2 doses of MenACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 3.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY3 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	-3
	Confidence Interval	(2-Sided) 95%; -11.9 to 6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 3.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY4 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	5.3
	Confidence Interval	(2-Sided) 95%; -3.3 to 13.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 2 doses of MenACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 4.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY3 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -7.5 to 2.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 4.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY4 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -4.4 to 4.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 2 doses of MenACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 5.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY3 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	-4.3
	Confidence Interval	(2-Sided) 95%; -12.1 to 3.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 5.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY4 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	4.9
	Confidence Interval	(2-Sided) 95%; -1.9 to 11.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 2 doses of MenACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 6A.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY3 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -3.7 to 3.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 6A.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY4 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; -2.2 to 4.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 2 doses of MenACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 6B.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY3 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -8.4 to 7.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 6B.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY4 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	10.2
	Confidence Interval	(2-Sided) 95%; 3.4 to 17.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 2 doses of MenACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 7F.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY3 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -1.7 to 3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 7F.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY4 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -2.1 to 3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 2 doses of MenACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 9V.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY3 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	-3.1
	Confidence Interval	(2-Sided) 95%; -9.7 to 3.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 9V.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY4 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	4
	Confidence Interval	(2-Sided) 95%; -1.5 to 9.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 2 doses of MenACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 14.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY3 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	vaccine group difference
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95%; -1.2 to 5.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of MenACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 14.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY3 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	2.5
	Confidence Interval	(2-Sided) 95%; -0.2 to 6.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 2 doses of MenACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 18C.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY3 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -6.3 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 18C.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY4 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) 95%; -6.2 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 2 doses of MenACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 19A.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY3 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -7.1 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 19A.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY4 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	-5.5
	Confidence Interval	(2-Sided) 95%; -11.3 to -0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 2 doses of MenACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 19F.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY3 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -1.7 to 3.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 19F.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY4 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -2.1 to 3.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 2 doses of MenACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 23F.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY3 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95%; -4.2 to 8.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 7 months of age for Serotype 23F.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI for the between group difference (MenACWY4 minus Routine) in percentage of subjects with IgG concentration ≥ 0.35 μg/mL against each pneumococcal anti-capsular polysaccharide is greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine group difference
	Estimated Value	4.5
	Confidence Interval	(2-Sided) 95%; -1.4 to 10.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Effect of Concomitant Administration of 3 or 4 Doses of MenACWY on Immune Response to PCV-13 Antigens at 13 Months of Age.
Description	Geometric mean concentrations (GMCs) of antibodies against PCV-13 vaccine antigens at 13 months of age following concomitant administration of a 3- or 4-dose series of MenACWY with PCV-13.
Time Frame	13 months of age.

Outcome Measure Data

Analysis Population Description

Analysis was done on the Toddler PPS.

Arm/Group Title	MenACWY3	MenACWY4	Routine Vaccines
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	Subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.	Subjects received routine vaccines only, including PCV-13, at 2, 4, 6 and 12 months of age.
Measure Participants	147	117	124
1 (N=145,116,123)	2	2.16	2.14
3 (N=139,113,118)	0.88	0.97	0.77
4 (N=146,117,123)	1.19	1.45	1.53
5 (N=140,114,117)	1.29	1.35	1.26
6A (N=146,117,124)	6.89	9.01	8.16
6B (N=147,117,124)	4.29	5.23	5.04
7F (N=147,116,123)	3.96	5.14	4.95
9V (N=146,117,123)	1.37	1.85	1.73
14 (N=147,117,124)	7.76	7.86	7.54
18C (N=146,116,123)	1.52	2.34	2.13
19A (N=144,114,124)	5.51	5.23	5.39
19F (N=147,117,124)	5.79	6.19	5.8
23F (N=147,117,124)	4.21	4.84	5.44

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 1.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between groups (MenACWY3 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 4 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 1.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between the groups (MenACWY4 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 3.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between groups (MenACWY3 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.93 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 4 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 3.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between the groups (MenACWY4 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95%; 1.01 to 1.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 4.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between groups (MenACWY3 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.62 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 4 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 4.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between the groups (MenACWY4 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 5.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between groups (MenACWY3 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 4 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 5.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between the groups (MenACWY4 to routine vaccines) is greater than 0.5
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 6A.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between groups (MenACWY3 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 4 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 6A.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between the groups (MenACWY4 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 6B.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between groups (MenACWY3 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 4 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 6B.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between the groups (MenACWY4 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 7F.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between groups (MenACWY3 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; 0.67 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 4 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 7F.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between the groups (MenACWY4 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 9V.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between groups (MenACWY3 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.66 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 4 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 9V.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between the groups (MenACWY4 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 14.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between groups (MenACWY3 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 4 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 14.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between the groups (MenACWY4 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 18C.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between groups (MenACWY3 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.59 to 0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 4 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 18C.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between the groups (MenACWY4 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 19A.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between groups (MenACWY3 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 4 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 19A.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between the groups (MenACWY4 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 19F.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between groups (MenACWY3 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1
	Confidence Interval	(2-Sided) 95%; 0.82 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 4 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 19F.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between the groups (MenACWY4 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 3 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 23F.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between groups (MenACWY3 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.62 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	MenACWY4, Routine Vaccines
	Comments	To demonstrate non-inferiority of immune response to PCV-13 antigens after concomitant administration of 4 doses of Men ACWY with routine vaccines including PCV-13, versus administration of routine vaccines only, at 13 months of age for Serotype 23F.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority will be concluded if the lower limit of the two-sided 95% CI around the ratio of GMCs between the groups (MenACWY4 to routine vaccines) is greater than 0.5.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.7 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percentage Of Subjects Reporting at Least One Severe Systemic Solicited Adverse Event.
Description	Safety was assessed as the percentages of subjects who reported severe solicited systemic adverse events within 30 minutes through day 7 of MenACWY administration with concomitant vaccines vs. concomitant vaccines alone.
Time Frame	Within 7 days

Outcome Measure Data

Analysis Population Description

Analysis was done on the Solicited Safety Set - All subjects in the Exposed Set with solicited adverse event data

Arm/Group Title	MenACWY3	MenACWY4	Routine Vaccines
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	Subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.	Subjects received routine vaccines only, including PCV-13, at 2, 4, 6 and 12 months of age.
Measure Participants	238	240	230
Number [Percentage of subjects]	18	21	18

12. Secondary Outcome

Title	Number Of Subjects Reporting Solicited Local or Systemic Adverse Events.
Description	Safety was assessed as the number of subjects who reported solicited local or systemic adverse events between 6 hours and day 7 after administration of MenACWY with concomitant vaccines vs. concomitant vaccines alone.
Time Frame	Day 1 through Day 7

Outcome Measure Data

Analysis Population Description

Analysis was done on Solicited Safety Set - All subjects in the Exposed Set with solicited adverse event data

Arm/Group Title	MenACWY3	MenACWY4	Routine Vaccines
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	Subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.	Subjects received routine vaccines only, including PCV-13, at 2, 4, 6 and 12 months of age.
Measure Participants	238	239	229
Injection site erythema	72	64	79
Injection site induration	60	40	74
Tenderness	117	127	126
Change in eating habits (N=238,238,229)	104	104	93
Sleepiness	153	147	149
Persistent crying	140	137	112
Irritability	173	171	152
Vomiting	68	52	54
Diarrhea	89	69	68
Fever (≥38.0°C)	55	52	41
Rash	23	19	18
Use of analgesic/antipyretic	162	173	153

13. Secondary Outcome

Title	Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination.
Time Frame	13 months of age

Outcome Measure Data

Analysis Population Description

Analysis was done on the Unsolicited Safety Set - All subjects in the Exposed Set with unsolicited adverse event data.

Arm/Group Title	MenACWY3	MenACWY4	Routine Vaccines
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	Subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.	Subjects received routine vaccines only, including PCV-13, at 2, 4, 6 and 12 months of age.
Measure Participants	242	252	239
Any AE	219	220	209
At least possibly related AEs	24	32	10
SAEs	11	19	11
Deaths	0	0	1
Medically attended AEs	210	211	198
AEs resulting in premature withdrawal	1	2	2

Adverse Events

Time Frame	13 months of age
Adverse Event Reporting Description	Solicited local and systemic and unsolicited AEs were assessed for 7 days postvaccination. AEs and SAEs were assessed throughout the study period. Out of a total of 751 subjects enrolled in the study, 733 (98%) subjects were exposed to at least 1 study vaccination and provided safety information.
Arm/Group Title	MenACWY3		MenACWY4		Routine Vaccines
Arm/Group Description	Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.		Subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.		Subjects received routine vaccines only, including PCV-13, at 2, 4, 6 and 12 months of age.
All Cause Mortality
	MenACWY3		MenACWY4		Routine Vaccines
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	MenACWY3		MenACWY4		Routine Vaccines
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/242 (4.5%)		19/252 (7.5%)		11/239 (4.6%)
Cardiac disorders
Cardio-respiratory arrest	0/242 (0%)		0/252 (0%)		1/239 (0.4%)
Congenital, familial and genetic disorders
Congenital megacolon	0/242 (0%)		0/252 (0%)		1/239 (0.4%)
Krabbe's disease	1/242 (0.4%)		0/252 (0%)		0/239 (0%)
Laryngomalacia	0/242 (0%)		0/252 (0%)		1/239 (0.4%)
Gastrointestinal disorders
Anal fissure	0/242 (0%)		0/252 (0%)		1/239 (0.4%)
General disorders
Pyrexia	0/242 (0%)		1/252 (0.4%)		0/239 (0%)
Infections and infestations
Abdominal abscess	0/242 (0%)		1/252 (0.4%)		0/239 (0%)
Abscess	0/242 (0%)		1/252 (0.4%)		0/239 (0%)
Atypical pneumonia	0/242 (0%)		1/252 (0.4%)		0/239 (0%)
Bronchiolitis	2/242 (0.8%)		2/252 (0.8%)		4/239 (1.7%)
Clostridium difficile colitis	0/242 (0%)		1/252 (0.4%)		0/239 (0%)
Croup infectious	0/242 (0%)		0/252 (0%)		1/239 (0.4%)
Gastroenteritis	1/242 (0.4%)		0/252 (0%)		1/239 (0.4%)
Gastroenteritis viral	0/242 (0%)		1/252 (0.4%)		0/239 (0%)
Influenza	1/242 (0.4%)		0/252 (0%)		0/239 (0%)
Otitis media acute	0/242 (0%)		0/252 (0%)		1/239 (0.4%)
Pneumonia	1/242 (0.4%)		1/252 (0.4%)		0/239 (0%)
Pneumonia respiratory syncytial viral	0/242 (0%)		0/252 (0%)		1/239 (0.4%)
Rectal abscess	0/242 (0%)		1/252 (0.4%)		0/239 (0%)
Respiratory synctial virus bronchiolitis	2/242 (0.8%)		5/252 (2%)		2/239 (0.8%)
Staphylococcal abscess	1/242 (0.4%)		0/252 (0%)		0/239 (0%)
Injury, poisoning and procedural complications
Skull fracture	1/242 (0.4%)		0/252 (0%)		0/239 (0%)
Metabolism and nutrition disorders
Dehydration	1/242 (0.4%)		0/252 (0%)		0/239 (0%)
Failure to thrive	1/242 (0.4%)		0/252 (0%)		0/239 (0%)
Hyperkalaemia	0/242 (0%)		0/252 (0%)		1/239 (0.4%)
Nervous system disorders
Convulsion	0/242 (0%)		2/252 (0.8%)		0/239 (0%)
Hypoxic-ischaemic encephalopathy	0/242 (0%)		0/252 (0%)		1/239 (0.4%)
Nystagmus	0/242 (0%)		1/252 (0.4%)		0/239 (0%)
Psychiatric disorders
Breath holding	0/242 (0%)		1/252 (0.4%)		0/239 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/242 (0%)		1/252 (0.4%)		0/239 (0%)
Pneumomediastinum	1/242 (0.4%)		0/252 (0%)		0/239 (0%)
Pneumonitis	0/242 (0%)		0/252 (0%)		1/239 (0.4%)
Respiratory acidosis	0/242 (0%)		0/252 (0%)		1/239 (0.4%)
Sleep apnoea syndrome	0/242 (0%)		0/252 (0%)		1/239 (0.4%)
Other (Not Including Serious) Adverse Events
	MenACWY3		MenACWY4		Routine Vaccines
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	238/242 (98.3%)		233/252 (92.5%)		228/239 (95.4%)
Ear and labyrinth disorders
Ear pain	13/242 (5.4%)		10/252 (4%)		9/239 (3.8%)
Eye disorders
Conjunctivitis	42/242 (17.4%)		25/252 (9.9%)		40/239 (16.7%)
Gastrointestinal disorders
Constipation	10/242 (4.1%)		21/252 (8.3%)		19/239 (7.9%)
Diarrhea	103/242 (42.6%)		78/252 (31%)		80/239 (33.5%)
Gastrooesophageal reflux disease	11/242 (4.5%)		14/252 (5.6%)		27/239 (11.3%)
Teething	15/242 (6.2%)		13/252 (5.2%)		19/239 (7.9%)
Vomiting	76/242 (31.4%)		68/252 (27%)		67/239 (28%)
General disorders
Crying	140/242 (57.9%)		138/252 (54.8%)		112/239 (46.9%)
Injection site erythema	87/242 (36%)		80/252 (31.7%)		89/239 (37.2%)
Injection site induration	65/242 (26.9%)		45/252 (17.9%)		79/239 (33.1%)
Injection site pain	137/242 (56.6%)		140/252 (55.6%)		138/239 (57.7%)
Irritability	181/242 (74.8%)		179/252 (71%)		157/239 (65.7%)
Pyrexia	88/242 (36.4%)		87/252 (34.5%)		69/239 (28.9%)
Infections and infestations
Bronchiolitis	34/242 (14%)		36/252 (14.3%)		30/239 (12.6%)
Bronchitis	8/242 (3.3%)		19/252 (7.5%)		17/239 (7.1%)
Candida nappy rash	13/242 (5.4%)		6/252 (2.4%)		7/239 (2.9%)
Croup Infectious	13/242 (5.4%)		16/252 (6.3%)		16/239 (6.7%)
Gastroenteritis	22/242 (9.1%)		18/252 (7.1%)		27/239 (11.3%)
Otitis media	94/242 (38.8%)		77/252 (30.6%)		89/239 (37.2%)
Otitis media acute	23/242 (9.5%)		19/252 (7.5%)		16/239 (6.7%)
Rhinitis	20/242 (8.3%)		17/252 (6.7%)		15/239 (6.3%)
Sinusitis	9/242 (3.7%)		17/252 (6.7%)		7/239 (2.9%)
Upper respiratory tract infection	105/242 (43.4%)		107/252 (42.5%)		106/239 (44.4%)
Viral infection	38/242 (15.7%)		32/252 (12.7%)		30/239 (12.6%)
Viral rash	10/242 (4.1%)		10/252 (4%)		13/239 (5.4%)
Candidiasis	14/242 (5.8%)		20/252 (7.9%)		21/239 (8.8%)
Nervous system disorders
Somnolence	162/242 (66.9%)		154/252 (61.1%)		158/239 (66.1%)
Psychiatric disorders
Eating disorder	104/242 (43%)		104/252 (41.3%)		93/239 (38.9%)
Respiratory, thoracic and mediastinal disorders
Cough	32/242 (13.2%)		32/252 (12.7%)		37/239 (15.5%)
Nasal congestion	16/242 (6.6%)		18/252 (7.1%)		14/239 (5.9%)
Wheezing	12/242 (5%)		9/252 (3.6%)		16/239 (6.7%)
Skin and subcutaneous tissue disorders
Dermatitis atopic	10/242 (4.1%)		11/252 (4.4%)		14/239 (5.9%)
Dermatitis diaper	38/242 (15.7%)		31/252 (12.3%)		22/239 (9.2%)
Eczema	16/242 (6.6%)		19/252 (7.5%)		20/239 (8.4%)
Rash	29/242 (12%)		31/252 (12.3%)		35/239 (14.6%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.