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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

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ClinicalTrials.gov Identifier: NCT01214837
Recruitment Status : Completed
First Posted : October 5, 2010
Results First Posted : October 2, 2014
Last Update Posted : October 9, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Conditions Meningococcal Disease
Meningococcal Meningitis
Interventions Biological: MenACWY-CRM
Biological: Routine Vaccines
Enrollment 751
Recruitment Details Subjects were enrolled at 3 sites in Canada and 37 sites in United States of America.
Pre-assignment Details All the enrolled subjects were included in the trial.
Arm/Group Title MenACWY3 MenACWY4 Routine Vaccines
Hide 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
Reason Not Completed
Death             0             0             1
Adverse Event             1             2             1
Withdrawal by Subject             27             36             28
Lost to Follow-up             20             15             21
Inappropriate Enrolment             0             1             2
Administrative Reason             2             6             4
Protocol Violation             3             1             5
Unable to Classify             1             3             0
Arm/Group Title MenACWY3 MenACWY4 Routine Vaccines Total
Hide 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 Number of Baseline Participants 249 256 246 751
Hide Baseline Analysis Population Description
All enrolled population- All subjects who had signed an informed consent, undergone screening procedure(s) and were randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 249 participants 256 participants 246 participants 751 participants
66.4  (7.1) 66.7  (7.4) 66.7  (7.0) 66.6  (7.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 249 participants 256 participants 246 participants 751 participants
Female
126
  50.6%
123
  48.0%
106
  43.1%
355
  47.3%
Male
123
  49.4%
133
  52.0%
140
  56.9%
396
  52.7%
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.
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 152
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of subjects
Serogroup A (N=141)
96
(91 to 98)
Serogroup C
99
(95 to 100)
Serogroup W (N=138)
99
(96 to 100)
Serogroup Y (N=146)
99
(96 to 100)
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.
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on Toddler PPS.
Arm/Group Title MenACWY3 MenACWY4
Hide 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.
Overall Number of Participants Analyzed 160 152
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of subjects
Serogroup A (N=146,141)
88
(82 to 93)
96
(91 to 98)
Serogroup C
95
(90 to 98)
99
(95 to 100)
Serogroup W (N=153,138)
99
(96 to 100)
99
(96 to 100)
Serogroup Y (N=154,146)
100
(98 to 100)
99
(96 to 100)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value -7
Confidence Interval (2-Sided) 95%
-14 to -1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value -4
Confidence Interval (2-Sided) 95%
-8 to 0
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 0
Confidence Interval (2-Sided) 95%
-3 to 3
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 1
Confidence Interval (2-Sided) 95%
-2 to 4
Estimation Comments [Not Specified]
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.
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 185 176 187
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Serogroup A (baseline; N=0,0,166)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
4
(1 to 8)
Serogroup A (3 months; N=0,82,0)
NA [1] 
(NA to NA)
9
(4 to 17)
NA [1] 
(NA to NA)
Serogroup A (4 months; N=0,70,0)
NA [1] 
(NA to NA)
4
(1 to 12)
NA [1] 
(NA to NA)
Serogroup A (5 months; N=157,0,0)
43
(35 to 51)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Serogroup A (7 months; N=169,157,171)
23
(17 to 30)
84
(77 to 89)
1
(0.015 to 3)
Serogroup C (baseline; N=0,0,167)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
9
(5 to 14)
Serogroup C (3 months; N=0,85,0)
NA [1] 
(NA to NA)
28
(19 to 39)
NA [1] 
(NA to NA)
Serogroup C (4 months; N=0,70,0)
NA [1] 
(NA to NA)
41
(30 to 54)
NA [1] 
(NA to NA)
Serogroup C (5 months; N=170,0,0)
86
(80 to 91)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Serogroup C (7 months)
71
(64 to 78)
95
(91 to 98)
1
(0.014 to 3)
Serogroup W (baseline; N=0,0,157)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
20
(14 to 28)
Serogroup W (3 months; N=0,84,0)
NA [1] 
(NA to NA)
15
(9 to 25)
NA [1] 
(NA to NA)
Serogroup W (4 months; N=0,71,0)
NA [1] 
(NA to NA)
35
(24 to 47)
NA [1] 
(NA to NA)
Serogroup W (5 months; N=162,0,0)
86
(80 to 91)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Serogroup W (7 months; N=179,162,181)
74
(67 to 81)
99
(96 to 100)
1
(0.014 to 3)
Serogroup Y (baseline; N=0,0,150)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
7
(4 to 13)
Serogroup Y (3 months; N=0,80,0)
NA [1] 
(NA to NA)
8
(3 to 16)
NA [1] 
(NA to NA)
Serogroup Y (4 months; N=0,69,0)
NA [1] 
(NA to NA)
7
(2 to 16)
NA [1] 
(NA to NA)
Serogroup Y (5 months; N=152,0,0)
67
(59 to 75)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Serogroup Y (7 months; N=170,163,173)
48
(40 to 55)
94
(90 to 97)
0
(0 to 2)
[1]
Data was not collected at this timepoint
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.
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the Infant PPS.
Arm/Group Title MenACWY3 MenACWY4 Routine Vaccines
Hide 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.
Overall Number of Participants Analyzed 185 176 187
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
Serogroup A (baseline; N=0,0,166)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
2.18
(2.05 to 2.33)
Serogroup A (3 months; N=0,82,0)
NA [1] 
(NA to NA)
2.63
(2.2 to 3.15)
NA [1] 
(NA to NA)
Serogroup A (4 months; N=0,70,0)
NA [1] 
(NA to NA)
2.18
(2 to 2.37)
NA [1] 
(NA to NA)
Serogroup A (5 months; N=157,0,0)
7.09
(5.62 to 8.94)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Serogroup A (7 months; N=169,157,171)
3.68
(3.17 to 4.29)
28
(23 to 35)
2.02
(1.98 to 2.06)
Serogroup C (baseline; N=0,0,167)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
2.52
(2.28 to 2.78)
Serogroup C (3 months; N=0,85,0)
NA [1] 
(NA to NA)
4.79
(3.71 to 6.19)
NA [1] 
(NA to NA)
Serogroup C (4 months; N=0,70,0)
NA [1] 
(NA to NA)
6.44
(4.83 to 8.59)
NA [1] 
(NA to NA)
Serogroup C (5 months; N=170,0,0)
50
(39 to 64)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Serogroup C (7 months)
17
(14 to 22)
86
(70 to 104)
2.03
(1.97 to 2.08)
Serogroup W (baseline; N=0,0,157)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
3.32
(2.82 to 3.9)
Serogroup W (3 months; N=0,84,0)
NA [1] 
(NA to NA)
3
(2.48 to 3.61)
NA [1] 
(NA to NA)
Serogroup W (4 months;N=0,71,0)
NA [1] 
(NA to NA)
4.38
(3.42 to 5.61)
NA [1] 
(NA to NA)
Serogroup W (5 months; N=162,0,0)
55
(42 to 71)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Serogroup W (7 months; N=179,162,181)
17
(14 to 21)
90
(77 to 104)
2.04
(1.96 to 2.11)
Serogroup Y (baseline; N=0,0,150)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
2.47
(2.25 to 2.7)
Serogroup Y (3 months; N=0,80,0)
NA [1] 
(NA to NA)
2.5
(2.14 to 2.93)
NA [1] 
(NA to NA)
Serogroup Y (4 months; N=0,69,0)
NA [1] 
(NA to NA)
2.46
(2.16 to 2.79)
NA [1] 
(NA to NA)
Serogroup Y (5 months; N=152,0,0)
20
(15 to 26)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Serogroup Y (7 months; N=170,163,173)
7.56
(6.29 to 9.08)
52
(43 to 64)
2
(2 to 2)
[1]
Data was not collected at this timepoint
5.Secondary Outcome
Title Percentage of Subjects With hSBA ≥1:8 Following 2 and 3 Infant Doses of MenACWY.
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the Toddler PPS.
Arm/Group Title MenACWY3 MenACWY4
Hide 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.
Overall Number of Participants Analyzed 149 147
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of subjects
Serogroup A (N=141,138)
6
(2 to 11)
22
(15 to 30)
Serogroup C
19
(13 to 27)
48
(39 to 56)
Serogroup W (N=149,142)
33
(25 to 41)
66
(58 to 74)
Serogroup Y (N=145,139)
25
(18 to 33)
55
(47 to 64)
6.Secondary Outcome
Title Geometric Mean hSBA Titers Following 2 and 3 Infant Doses of MenACWY.
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the Toddler PPS.
Arm/Group Title MenACWY3 MenACWY4
Hide 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.
Overall Number of Participants Analyzed 149 147
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
Serogroup A (N=141,138)
2.28
(2.09 to 2.49)
3.65
(3.08 to 4.33)
Serogroup C
3.54
(2.99 to 4.17)
8.55
(6.75 to 11)
Serogroup W (N=149,142)
5.41
(4.39 to 6.67)
13
(11 to 16)
Serogroup Y (N=145,139)
3.82
(3.24 to 4.49)
9.65
(7.79 to 12)
7.Secondary Outcome
Title GMTs at 13 Months of Age After Completion of 3- and 4-Dose Series of MenACWY.
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the Toddler PPS.
Arm/Group Title MenACWY3 MenACWY4
Hide 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.
Overall Number of Participants Analyzed 160 152
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
Serogroup A (N=146,141)
59
(45 to 77)
94
(76 to 117)
Serogroup C
124
(99 to 156)
160
(130 to 198)
Serogroup W (N=153,138)
248
(202 to 303)
244
(195 to 305)
Serogroup Y (N=154,146)
212
(175 to 258)
254
(203 to 318)
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.
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the Toddler PPS.
Arm/Group Title MenACWY3 MenACWY4
Hide 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.
Overall Number of Participants Analyzed 147 147
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of subjects
Serogroup A (N=127,129)
88
(81 to 93)
95
(90 to 98)
Serogroup C
93
(88 to 97)
91
(85 to 95)
Serogroup W (N=140,131)
98
(94 to 100)
90
(84 to 95)
Serogroup Y (N=139,136)
100
(97 to 100)
96
(91 to 98)
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.
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the Infant PPS.
Arm/Group Title MenACWY3 MenACWY4 Routine Vaccines
Hide 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.
Overall Number of Participants Analyzed 160 137 158
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of subjects
1 (N=159,136,156)
93.7
(88.7 to 96.9)
100
(97.3 to 100)
94.2
(89.3 to 97.3)
3 (N=150,129,147)
79.3
(72 to 85.5)
87.6
(80.6 to 92.7)
82.3
(75.2 to 88.1)
4 (N=160,137,157)
94.4
(89.6 to 97.4)
97.1
(92.7 to 99.2)
96.8
(92.7 to 99)
5 (N=156,133,154)
84
(77.3 to 89.4)
93.2
(87.5 to 96.9)
88.3
(82.2 to 92.9)
6A (N=159,136,156)
98.1
(94.6 to 99.6)
99.3
(96 to 100)
98.1
(94.5 to 99.6)
6B (N=160,137,157)
84.4
(77.8 to 89.6)
94.9
(89.8 to 97.9)
84.7
(78.1 to 90)
7F (N=158,136,156)
100
(97.7 to 100)
100
(97.3 to 100)
99.4
(96.5 to 100)
9V (N=159,136,157)
89.3
(83.4 to 93.6)
96.3
(91.6 to 98.8)
92.4
(87 to 96)
14 (N=158,136,158)
99.4
(96.5 to 100)
100
(97.3 to 100)
97.5
(93.6 to 99.3)
18C (N=158,136,157)
97.5
(93.6 to 99.3)
97.8
(93.7 to 99.5)
100
(97.7 to 100)
19A (N=158,135,156)
95.6
(91.1 to 98.2)
92.6
(86.8 to 96.4)
98.1
(94.5 to 99.6)
19F (N=159,136,158)
100
(97.7 to 100)
100
(97.3 to 100)
99.4
(96.5 to 100)
23F (N=158,136,158)
93
(87.9 to 96.5)
95.6
(90.6 to 98.4)
91.1
(85.6 to 95.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-6.1 to 5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 5.8
Confidence Interval (2-Sided) 95%
3 to 10.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value -3
Confidence Interval (2-Sided) 95%
-11.9 to 6
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 5.3
Confidence Interval (2-Sided) 95%
-3.3 to 13.7
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-7.5 to 2.3
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-4.4 to 4.7
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value -4.3
Confidence Interval (2-Sided) 95%
-12.1 to 3.4
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 4.9
Confidence Interval (2-Sided) 95%
-1.9 to 11.8
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-3.7 to 3.8
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-2.2 to 4.8
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-8.4 to 7.7
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 10.2
Confidence Interval (2-Sided) 95%
3.4 to 17.2
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-1.7 to 3.5
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-2.1 to 3.5
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value -3.1
Confidence Interval (2-Sided) 95%
-9.7 to 3.4
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 4
Confidence Interval (2-Sided) 95%
-1.5 to 9.7
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter vaccine group difference
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
-1.2 to 5.7
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 2.5
Confidence Interval (2-Sided) 95%
-0.2 to 6.3
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-6.3 to -0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-6.2 to 0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-7.1 to 1.6
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value -5.5
Confidence Interval (2-Sided) 95%
-11.3 to -0.9
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-1.7 to 3.4
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-2.1 to 3.4
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
-4.2 to 8.2
Estimation Comments [Not Specified]
Show Statistical Analysis 26 Hide 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 [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine group difference
Estimated Value 4.5
Confidence Interval (2-Sided) 95%
-1.4 to 10.5
Estimation Comments [Not Specified]
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.
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the Toddler PPS.
Arm/Group Title MenACWY3 MenACWY4 Routine Vaccines
Hide 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.
Overall Number of Participants Analyzed 147 117 124
Geometric Mean (95% Confidence Interval)
Unit of Measure: µg/mL
1 (N=145,116,123)
2
(1.7 to 2.36)
2.16
(1.83 to 2.56)
2.14
(1.8 to 2.54)
3 (N=139,113,118)
0.88
(0.74 to 1.05)
0.97
(0.81 to 1.15)
0.77
(0.64 to 0.93)
4 (N=146,117,123)
1.19
(0.99 to 1.42)
1.45
(1.21 to 1.75)
1.53
(1.27 to 1.86)
5 (N=140,114,117)
1.29
(1.11 to 1.49)
1.35
(1.16 to 1.57)
1.26
(1.08 to 1.48)
6A (N=146,117,124)
6.89
(5.78 to 8.21)
9.01
(7.52 to 11)
8.16
(6.77 to 9.82)
6B (N=147,117,124)
4.29
(3.6 to 5.11)
5.23
(4.36 to 6.27)
5.04
(4.18 to 6.08)
7F (N=147,116,123)
3.96
(3.42 to 4.58)
5.14
(4.41 to 5.98)
4.95
(4.23 to 5.78)
9V (N=146,117,123)
1.37
(1.17 to 1.61)
1.85
(1.56 to 2.18)
1.73
(1.46 to 2.05)
14 (N=147,117,124)
7.76
(6.51 to 9.26)
7.86
(6.55 to 9.43)
7.54
(6.25 to 9.09)
18C (N=146,116,123)
1.52
(1.28 to 1.8)
2.34
(1.96 to 2.79)
2.13
(1.78 to 2.55)
19A (N=144,114,124)
5.51
(4.61 to 6.6)
5.23
(4.34 to 6.3)
5.39
(4.45 to 6.51)
19F (N=147,117,124)
5.79
(4.9 to 6.85)
6.19
(5.21 to 7.35)
5.8
(4.86 to 6.92)
23F (N=147,117,124)
4.21
(3.49 to 5.09)
4.84
(3.98 to 5.89)
5.44
(4.45 to 6.65)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.77 to 1.13
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.83 to 1.25
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.93 to 1.4
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
1.01 to 1.55
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.62 to 0.96
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.75 to 1.18
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.86 to 1.21
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.89 to 1.29
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.69 to 1.04
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
0.88 to 1.37
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.69 to 1.05
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.83 to 1.3
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
0.67 to 0.95
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.87 to 1.25
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.66 to 0.96
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.87 to 1.31
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.84 to 1.27
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.83 to 1.3
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.59 to 0.87
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
0.89 to 1.36
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.83 to 1.27
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.77 to 1.21
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1
Confidence Interval (2-Sided) 95%
0.82 to 1.22
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.86 to 1.32
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection MenACWY3, 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.62 to 0.97
Estimation Comments [Not Specified]
Show Statistical Analysis 26 Hide 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 [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter GMC ratio
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.7 to 1.13
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percentage Of Subjects Reporting at Least One Severe Systemic Solicited Adverse Event.
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 238 240 230
Measure Type: Number
Unit of Measure: Percentage of subjects
18 21 18
12.Secondary Outcome
Title Number Of Subjects Reporting Solicited Local or Systemic Adverse Events.
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 238 239 229
Measure Type: Number
Unit of Measure: Subjects
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.
Hide Description [Not Specified]
Time Frame 13 months of age
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 242 252 239
Measure Type: Number
Unit of Measure: Subjects
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
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
MenACWY3 MenACWY4 Routine Vaccines
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/242 (4.55%)   19/252 (7.54%)   11/239 (4.60%) 
Cardiac disorders       
Cardio-respiratory arrest * 1  0/242 (0.00%)  0/252 (0.00%)  1/239 (0.42%) 
Congenital, familial and genetic disorders       
Congenital megacolon * 1  0/242 (0.00%)  0/252 (0.00%)  1/239 (0.42%) 
Krabbe's disease * 1  1/242 (0.41%)  0/252 (0.00%)  0/239 (0.00%) 
Laryngomalacia * 1  0/242 (0.00%)  0/252 (0.00%)  1/239 (0.42%) 
Gastrointestinal disorders       
Anal fissure * 1  0/242 (0.00%)  0/252 (0.00%)  1/239 (0.42%) 
General disorders       
Pyrexia  1  0/242 (0.00%)  1/252 (0.40%)  0/239 (0.00%) 
Infections and infestations       
Abdominal abscess * 1  0/242 (0.00%)  1/252 (0.40%)  0/239 (0.00%) 
Abscess * 1  0/242 (0.00%)  1/252 (0.40%)  0/239 (0.00%) 
Atypical pneumonia * 1  0/242 (0.00%)  1/252 (0.40%)  0/239 (0.00%) 
Bronchiolitis * 1  2/242 (0.83%)  2/252 (0.79%)  4/239 (1.67%) 
Clostridium difficile colitis * 1  0/242 (0.00%)  1/252 (0.40%)  0/239 (0.00%) 
Croup infectious * 1  0/242 (0.00%)  0/252 (0.00%)  1/239 (0.42%) 
Gastroenteritis * 1  1/242 (0.41%)  0/252 (0.00%)  1/239 (0.42%) 
Gastroenteritis viral * 1  0/242 (0.00%)  1/252 (0.40%)  0/239 (0.00%) 
Influenza * 1  1/242 (0.41%)  0/252 (0.00%)  0/239 (0.00%) 
Otitis media acute * 1  0/242 (0.00%)  0/252 (0.00%)  1/239 (0.42%) 
Pneumonia * 1  1/242 (0.41%)  1/252 (0.40%)  0/239 (0.00%) 
Pneumonia respiratory syncytial viral * 1  0/242 (0.00%)  0/252 (0.00%)  1/239 (0.42%) 
Rectal abscess * 1  0/242 (0.00%)  1/252 (0.40%)  0/239 (0.00%) 
Respiratory synctial virus bronchiolitis * 1  2/242 (0.83%)  5/252 (1.98%)  2/239 (0.84%) 
Staphylococcal abscess * 1  1/242 (0.41%)  0/252 (0.00%)  0/239 (0.00%) 
Injury, poisoning and procedural complications       
Skull fracture * 1  1/242 (0.41%)  0/252 (0.00%)  0/239 (0.00%) 
Metabolism and nutrition disorders       
Dehydration * 1  1/242 (0.41%)  0/252 (0.00%)  0/239 (0.00%) 
Failure to thrive * 1  1/242 (0.41%)  0/252 (0.00%)  0/239 (0.00%) 
Hyperkalaemia * 1  0/242 (0.00%)  0/252 (0.00%)  1/239 (0.42%) 
Nervous system disorders       
Convulsion * 1  0/242 (0.00%)  2/252 (0.79%)  0/239 (0.00%) 
Hypoxic-ischaemic encephalopathy * 1  0/242 (0.00%)  0/252 (0.00%)  1/239 (0.42%) 
Nystagmus * 1  0/242 (0.00%)  1/252 (0.40%)  0/239 (0.00%) 
Psychiatric disorders       
Breath holding * 1  0/242 (0.00%)  1/252 (0.40%)  0/239 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Asthma * 1  0/242 (0.00%)  1/252 (0.40%)  0/239 (0.00%) 
Pneumomediastinum * 1  1/242 (0.41%)  0/252 (0.00%)  0/239 (0.00%) 
Pneumonitis * 1  0/242 (0.00%)  0/252 (0.00%)  1/239 (0.42%) 
Respiratory acidosis * 1  0/242 (0.00%)  0/252 (0.00%)  1/239 (0.42%) 
Sleep apnoea syndrome * 1  0/242 (0.00%)  0/252 (0.00%)  1/239 (0.42%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
MenACWY3 MenACWY4 Routine Vaccines
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   238/242 (98.35%)   233/252 (92.46%)   228/239 (95.40%) 
Ear and labyrinth disorders       
Ear pain * 1  13/242 (5.37%)  10/252 (3.97%)  9/239 (3.77%) 
Eye disorders       
Conjunctivitis * 1  42/242 (17.36%)  25/252 (9.92%)  40/239 (16.74%) 
Gastrointestinal disorders       
Constipation * 1  10/242 (4.13%)  21/252 (8.33%)  19/239 (7.95%) 
Diarrhea  1  103/242 (42.56%)  78/252 (30.95%)  80/239 (33.47%) 
Gastrooesophageal reflux disease * 1  11/242 (4.55%)  14/252 (5.56%)  27/239 (11.30%) 
Teething * 1  15/242 (6.20%)  13/252 (5.16%)  19/239 (7.95%) 
Vomiting  1  76/242 (31.40%)  68/252 (26.98%)  67/239 (28.03%) 
General disorders       
Crying  1  140/242 (57.85%)  138/252 (54.76%)  112/239 (46.86%) 
Injection site erythema  1  87/242 (35.95%)  80/252 (31.75%)  89/239 (37.24%) 
Injection site induration  1  65/242 (26.86%)  45/252 (17.86%)  79/239 (33.05%) 
Injection site pain  1  137/242 (56.61%)  140/252 (55.56%)  138/239 (57.74%) 
Irritability  1  181/242 (74.79%)  179/252 (71.03%)  157/239 (65.69%) 
Pyrexia  1  88/242 (36.36%)  87/252 (34.52%)  69/239 (28.87%) 
Infections and infestations       
Bronchiolitis * 1  34/242 (14.05%)  36/252 (14.29%)  30/239 (12.55%) 
Bronchitis * 1  8/242 (3.31%)  19/252 (7.54%)  17/239 (7.11%) 
Candida nappy rash * 1  13/242 (5.37%)  6/252 (2.38%)  7/239 (2.93%) 
Croup Infectious * 1  13/242 (5.37%)  16/252 (6.35%)  16/239 (6.69%) 
Gastroenteritis * 1  22/242 (9.09%)  18/252 (7.14%)  27/239 (11.30%) 
Otitis media * 1  94/242 (38.84%)  77/252 (30.56%)  89/239 (37.24%) 
Otitis media acute * 1  23/242 (9.50%)  19/252 (7.54%)  16/239 (6.69%) 
Rhinitis * 1  20/242 (8.26%)  17/252 (6.75%)  15/239 (6.28%) 
Sinusitis * 1  9/242 (3.72%)  17/252 (6.75%)  7/239 (2.93%) 
Upper respiratory tract infection * 1  105/242 (43.39%)  107/252 (42.46%)  106/239 (44.35%) 
Viral infection * 1  38/242 (15.70%)  32/252 (12.70%)  30/239 (12.55%) 
Viral rash * 1  10/242 (4.13%)  10/252 (3.97%)  13/239 (5.44%) 
Candidiasis * 1  14/242 (5.79%)  20/252 (7.94%)  21/239 (8.79%) 
Nervous system disorders       
Somnolence  1  162/242 (66.94%)  154/252 (61.11%)  158/239 (66.11%) 
Psychiatric disorders       
Eating disorder  1  104/242 (42.98%)  104/252 (41.27%)  93/239 (38.91%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  32/242 (13.22%)  32/252 (12.70%)  37/239 (15.48%) 
Nasal congestion * 1  16/242 (6.61%)  18/252 (7.14%)  14/239 (5.86%) 
Wheezing * 1  12/242 (4.96%)  9/252 (3.57%)  16/239 (6.69%) 
Skin and subcutaneous tissue disorders       
Dermatitis atopic * 1  10/242 (4.13%)  11/252 (4.37%)  14/239 (5.86%) 
Dermatitis diaper * 1  38/242 (15.70%)  31/252 (12.30%)  22/239 (9.21%) 
Eczema * 1  16/242 (6.61%)  19/252 (7.54%)  20/239 (8.37%) 
Rash  1  29/242 (11.98%)  31/252 (12.30%)  35/239 (14.64%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Posting Director
Organization: Novartis Vaccines and Diagnostics
EMail: RegistryContactVaccinesUS@novartis.com
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Responsible Party: Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier: NCT01214837     History of Changes
Other Study ID Numbers: V59_36
First Submitted: September 27, 2010
First Posted: October 5, 2010
Results First Submitted: August 20, 2014
Results First Posted: October 2, 2014
Last Update Posted: October 9, 2018