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Trial record 4 of 11 for:    "Rubella" | "Heptavalent Pneumococcal Conjugate Vaccine"

Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Combined Measles-mumps-rubella (MMR) Vaccine in Children in Their Second Year of Life

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ClinicalTrials.gov Identifier: NCT01681992
Recruitment Status : Completed
First Posted : September 10, 2012
Results First Posted : August 17, 2018
Last Update Posted : August 17, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Measles
Mumps
Rubella
Interventions Biological: Priorix
Biological: M-M-R II
Biological: Varivax
Biological: Havrix
Biological: Prevnar 13
Enrollment 4538
Recruitment Details US sub-cohort: Subjects recruited in US and received Inv_MMR_Min or Inv_MMR_Med or Com_MMR (Lot 1 or 2) co-administered with Varivax (VV), Havrix (HAV) and Prevnar 13 (PCV-13) at Day 0. Non-US sub-cohort: Subjects recruited outside US and received Inv_MMR_Min or Inv_MMR_Med or Com_MMR (Lot 1 or 2) co-administered with VV and HAV at Day 0.
Pre-assignment Details 4538 subjects were registered in the study. 3 subjects were excluded because of invalid Informed Consent Forms and 19 subjects received a subject number but were not vaccinated. Therefore, the number of subjects started is 4516.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description Subjects received one dose of GlaxoSmithKline (GSK) Biologicals’ measles, mumps, rubella (MMR) vaccine, Priorix (Inv_MMR), from a minimum potency lot (Inv_MMR_Min), co-administered with Varivax (VV) and Havrix (HAV) vaccines at Day 0. All US subjects were also co-administered Prevnar 13 (PCV-13) vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively. Subjects received one dose of GlaxoSmithKline (GSK) Biologicals’ measles, mumps, rubella (MMR) vaccine, Priorix (Inv_MMR), from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with Varivax (VV) and Havrix (HAV) vaccines at Day 0. All US subjects were also co-administered Prevnar 13 (PCV-13) vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively. Subjects received one dose of M-M-R II (Com_MMR) vaccine (Lot 1 or Lot 2), co-administered with Varivax (VV) and Havrix (HAV) vaccines at Day 0. All US subjects were also co-administered Prevnar 13 (PCV-13) vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Period Title: Overall Study
Started 1493 1497 1526
Completed 1427 1427 1443
Not Completed 66 70 83
Reason Not Completed
Adverse Event             3             2             3
Lost to Follow-up             36             38             53
As Per Sponsor Decision             0             0             1
Protocol Violation             0             0             1
Withdrawal by Subject             27             30             25
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group Total
Hide Arm/Group Description Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively. Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively. Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively. Total of all reporting groups
Overall Number of Baseline Participants 1493 1497 1526 4516
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 1493 participants 1497 participants 1526 participants 4516 participants
12.6  (0.9) 12.6  (0.9) 12.6  (0.9) 12.6  (0.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1493 participants 1497 participants 1526 participants 4516 participants
Female
704
  47.2%
718
  48.0%
758
  49.7%
2180
  48.3%
Male
789
  52.8%
779
  52.0%
768
  50.3%
2336
  51.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1493 participants 1497 participants 1526 participants 4516 participants
African Heritage / African American 45 53 46 144
American Indian or Alaskan Native 2 1 1 4
Asian - Central/South Asian Heritage 1 0 2 3
Asian - East Asian Heritage 3 0 1 4
Asian - South East Asian Heritage 362 366 367 1095
Native Hawaiian or Other Pacific Islander 0 1 0 1
White - Arabic / North African Heritage 8 8 8 24
White - Caucasian / European Heritage 1017 1022 1052 3091
Other 55 46 49 150
1.Primary Outcome
Title Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by Enzyme-linked Immunosorbent Assay [ELISA])
Hide Description For measles virus, a seroresponse was defined as post-vaccination anti-measles virus antibody concentration equal or above [≥] 200 mIU/mL (ELISA) among subjects who were seronegative (antibody concentration less than [<] 150 mIU/mL) before dose 1. Criteria to demonstrate an acceptable immune response of Inv_MMR_Min/Inv_MMR_Med vaccine in terms of seroresponse rate for measles virus at Day 42: The lower limit of the two-sided 97.5% CI for the seroresponse rate of Inv_MMR_Min/Inv_MMR_Med was to be ≥ 90% for antibodies to measles virus.
Time Frame At Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
According-to-protocol (ATP) cohort for analysis of immunogenicity post dose 1: all eligible subjects with pre- & post-dose 1 serology results & were below assay cut-off for at least 1 vaccine antigen for MMR at pre-vaccination, did not meet elimination criteria up to Day 42 blood sample & complied with post-dose 1 blood sample schedule.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1361 1366 1378
Measure Type: Number
Number (97.5% Confidence Interval)
Unit of Measure: Percentage of subjects
Anti-measles ≥ 150 mIU/mL
90.9
(89.0 to 92.6)
94.3
(92.7 to 95.6)
96.5
(95.2 to 97.5)
Anti-measles ≥ 200 mIU/mL
90.8
(88.9 to 92.5)
94.2
(92.6 to 95.5)
96.3
(95.0 to 97.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Min Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Min vaccine compared to Com_MMR vaccine in terms of seroresponse rate to measles virus at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% confidence interval (CI) on the group difference (Inv_MMR_Min minus Com_MMR) in seroresponse rate should be ≥ -5% for antibodies to measles virus when tested with ELISA.
Method of Estimation Estimation Parameter Difference in seroresponse rate
Estimated Value -5.48
Confidence Interval (2-Sided) 97.5%
-7.65 to -3.43
Estimation Comments Asymptotic standardized 97.5% CI for the difference in seroresponse rate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Med Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Med vaccine compared to Com_MMR vaccine in terms of seroresponse rate to measles virus at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% confidence interval (CI) on the group difference (Inv_MMR_Med minus Com_MMR) in seroresponse rate should be ≥ -5% for antibodies to measles virus when tested with ELISA.
Method of Estimation Estimation Parameter Difference in seroresponse rate
Estimated Value -2.08
Confidence Interval (2-Sided) 97.5%
-3.96 to -0.27
Estimation Comments Asymptotic standardized 97.5% CI for the difference in seroresponse rate.
2.Primary Outcome
Title Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
Hide Description For mumps virus, a seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 10 EU/mL (ELISA) among subjects who were seronegative (antibody concentration < 5 EU/mL) before dose 1. Criteria to demonstrate an acceptable immune response of Inv_MMR_Min/Inv_MMR_Med vaccine in terms of seroresponse rate for mumps virus at Day 42: The lower limit of the two-sided 97.5% CI for the seroresponse rate of Inv_MMR_Min/Inv_MMR_Med was to be ≥ 90% for antibodies to mumps virus.
Time Frame At Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
ATP cohort for analysis of immunogenicity post dose 1: all eligible subjects with pre- & post-dose 1 serology results & were below assay cut-off for at least 1 vaccine antigen for MMR at pre-vaccination, did not meet elimination criteria up to Day 42 blood sample & complied with post-dose 1 blood sample schedule.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1161 1131 1155
Measure Type: Number
Number (97.5% Confidence Interval)
Unit of Measure: Percentage of subjects
Anti-mumps ≥ 5 EU/mL
99.1
(98.2 to 99.6)
99.0
(98.1 to 99.6)
99.2
(98.4 to 99.7)
Anti-mumps ≥ 10 EU/mL
97.4
(96.2 to 98.3)
97.3
(96.0 to 98.2)
97.8
(96.7 to 98.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Min Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Min vaccine compared to Com_MMR vaccine in terms of seroresponse rate to mumps virus at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% CI on the group difference (Inv_MMR_Min minus Com_MMR) in seroresponse rate should be ≥ -5% for antibodies to mumps virus when tested with ELISA.
Method of Estimation Estimation Parameter Difference in seroresponse rate
Estimated Value -0.42
Confidence Interval (2-Sided) 97.5%
-1.91 to 1.04
Estimation Comments Asymptotic standardized 97.5% CI for the difference in seroresponse rate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Med Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Med vaccine compared to Com_MMR vaccine in terms of seroresponse rate to mumps virus at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% CI on the group difference (Inv_MMR_Med minus Com_MMR) in seroresponse rate should be ≥ -5% for antibodies to mumps virus when tested with ELISA.
Method of Estimation Estimation Parameter Difference in seroresponse rate
Estimated Value -0.58
Confidence Interval (2-Sided) 97.5%
-2.11 to 0.91
Estimation Comments Asymptotic standardized 97.5% CI for the difference in seroresponse rate.
3.Primary Outcome
Title Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by Plaque Reduction Neutralization Test [PRNT])
Hide Description For mumps virus as measured by PRNT, a seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 4 End point Dilution 50% (ED50) (PRNT) among subjects who were seronegative (antibody concentration < 2.5 ED50) before dose 1.
Time Frame At Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
ATP cohort for analysis of immunogenicity post dose 1: all eligible subjects with pre- & post-dose 1 serology results & were below assay cut-off for at least 1 vaccine antigen for MMR at pre-vaccination, did not meet elimination criteria up to Day 42 blood sample & complied with post-dose 1 blood sample schedule.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1252 1265 1287
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of subjects
≥ 2.5 ED50
79.1
(76.7 to 81.3)
81.6
(79.3 to 83.7)
87.5
(85.6 to 89.2)
≥ 4 ED50
71.2
(68.6 to 73.7)
73.4
(70.8 to 75.8)
80.6
(78.3 to 82.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Min Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Min vaccine compared to Com_MMR vaccine in terms of seroresponse rate to mumps virus at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% CI on the group difference (Inv_MMR_Min minus Com_MMR) in seroresponse rate should be ≥ -10% for antibodies to mumps virus when tested with PRNT.
Method of Estimation Estimation Parameter Difference in seroresponse rate
Estimated Value -9.41
Confidence Interval (2-Sided) 97.5%
-13.20 to -5.62
Estimation Comments Asymptotic standardized 97.5% CI for the difference in seroresponse rate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Med Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Med vaccine compared to Com_MMR vaccine in terms of seroresponse rate to mumps virus at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% CI on the group difference (Inv_MMR_Med minus Com_MMR) in seroresponse rate should be ≥ -10% for antibodies to mumps virus when tested with PRNT.
Method of Estimation Estimation Parameter Difference in seroresponse rate
Estimated Value -7.22
Confidence Interval (2-Sided) 97.5%
-10.94 to -3.49
Estimation Comments Asymptotic standardized 97.5% CI for the difference in seroresponse rate.
4.Primary Outcome
Title Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
Hide Description For rubella virus, a seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥ 10 IU/mL (ELISA) among subjects who were seronegative (antibody concentration < 4 IU/mL) before dose 1. Criteria to demonstrate an acceptable immune response of Inv_MMR_Min/Inv_MMR_Med vaccine in terms of seroresponse rate for rubella virus at Day 42: The lower limit of the two-sided 97.5% CI for the seroresponse rate of Inv_MMR_Min/Inv_MMR_Med was to be ≥ 90% for antibodies to mumps virus.
Time Frame At Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
ATP cohort for analysis of immunogenicity post dose 1: all eligible subjects with pre- & post-dose 1 serology results & were below assay cut-off for at least 1 vaccine antigen for MMR at pre-vaccination, did not meet elimination criteria up to Day 42 blood sample & complied with post-dose 1 blood sample schedule.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1359 1366 1376
Measure Type: Number
Number (97.5% Confidence Interval)
Unit of Measure: Percentage of subjects
≥ 4 IU/mL
99.3
(98.6 to 99.7)
99.5
(98.9 to 99.8)
99.5
(98.9 to 99.8)
≥ 10 IU/mL
96.8
(95.5 to 97.7)
97.3
(96.1 to 98.2)
98.5
(97.6 to 99.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Min Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Min vaccine compared to Com_MMR vaccine in terms of seroresponse rate to rubella virus at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% CI on the group difference (Inv_MMR_Min minus Com_MMR) in seroresponse rate should be ≥ -5% for antibodies to rubella virus when tested with ELISA.
Method of Estimation Estimation Parameter Difference in seroresponse rate
Estimated Value -1.71
Confidence Interval (2-Sided) 97.5%
-3.11 to -0.42
Estimation Comments Asymptotic standardized 97.5% CI for the difference in seroresponse rate.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Med Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Med vaccine compared to Com_MMR vaccine in terms of seroresponse rate to rubella virus at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% CI on the group difference (Inv_MMR_Med minus Com_MMR) in seroresponse rate should be ≥ -5% for antibodies to rubella virus when tested with ELISA.
Method of Estimation Estimation Parameter Difference in seroresponse rate
Estimated Value -1.18
Confidence Interval (2-Sided) 97.5%
-2.50 to 0.05
Estimation Comments Asymptotic standardized 97.5% CI for the difference in seroresponse rate.
5.Primary Outcome
Title Anti-measles Virus Antibody Concentrations (by ELISA)
Hide Description Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL.
Time Frame At Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
ATP cohort for analysis of immunogenicity post dose 1: all eligible subjects with pre- & post-dose 1 serology results & were below assay cut-off for at least 1 vaccine antigen for MMR at pre-vaccination, did not meet elimination criteria up to Day 42 blood sample & complied with post-dose 1 blood sample schedule.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1361 1366 1378
Geometric Mean (97.5% Confidence Interval)
Unit of Measure: mIU/mL
2209.9
(2041.3 to 2392.4)
2540.9
(2368.8 to 2725.5)
2787.7
(2619.5 to 2966.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Min Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Min vaccine compared to COM_MMR vaccine in terms of GMCs for anti-measles antibodies at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% CI on the group ratio of GMCs (Inv_MMR_Min over pooled Com_MMR) should to be ≥ 0.67 for antibodies to measles virus when tested with ELISA.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments 97.5% CI for GMC ratio was computed using ANOVA model on the log-transformed concentrations with vaccine group and the country as fixed effects.
Method of Estimation Estimation Parameter Adjusted GMC ratio
Estimated Value 0.79
Confidence Interval (2-Sided) 97.5%
0.72 to 0.88
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Med Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Med vaccine compared to COM_MMR vaccine in terms of GMCs for anti-measles antibodies at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% CI on the group ratio of GMCs (Inv_MMR_Med over pooled Com_MMR) should to be ≥ 0.67 for antibodies to measles virus when tested with ELISA.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments 97.5% CI for GMC ratio was computed using ANOVA model on the log-transformed concentrations with vaccine group and the country as fixed effects.
Method of Estimation Estimation Parameter Adjusted GMC ratio
Estimated Value 0.91
Confidence Interval (2-Sided) 97.5%
0.83 to 1.01
Estimation Comments [Not Specified]
6.Primary Outcome
Title Anti-mumps Virus Antibody Concentrations (by ELISA)
Hide Description Antibody concentrations were expressed as GMCs in EU/mL.
Time Frame At Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
ATP cohort for analysis of immunogenicity post dose 1: all eligible subjects with pre- & post-dose 1 serology results & were below assay cut-off for at least 1 vaccine antigen for MMR at pre-vaccination, did not meet elimination criteria up to Day 42 blood sample & complied with post-dose 1 blood sample schedule.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1161 1131 1155
Geometric Mean (97.5% Confidence Interval)
Unit of Measure: EU/mL
58.7
(55.5 to 62.1)
60.2
(56.8 to 63.7)
71.6
(67.7 to 75.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Min Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Min vaccine compared to COM_MMR vaccine in terms of GMCs for anti-mumps antibodies at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% CI on the group ratio of GMCs (Inv_MMR_Min over pooled Com_MMR) should to be ≥ 0.67 for antibodies to mumps virus when tested with ELISA.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments 97.5% CI for GMC ratio was computed using ANOVA model on the log-transformed concentrations with vaccine group and the country as fixed effects.
Method of Estimation Estimation Parameter Adjusted GMC ratio
Estimated Value 0.82
Confidence Interval (2-Sided) 97.5%
0.76 to 0.89
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Med Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Med vaccine compared to COM_MMR vaccine in terms of GMCs for anti-mumps antibodies at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% CI on the group ratio of GMCs (Inv_MMR_Med over pooled Com_MMR) should to be ≥ 0.67 for antibodies to mumps virus when tested with ELISA.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments 97.5% CI for GMC ratio was computed using ANOVA model on the log-transformed concentrations with vaccine group and the country as fixed effects.
Method of Estimation Estimation Parameter Adjusted GMC ratio
Estimated Value 0.84
Confidence Interval (2-Sided) 97.5%
0.78 to 0.91
Estimation Comments [Not Specified]
7.Primary Outcome
Title Anti-mumps Virus Antibody Concentrations (by PRNT)
Hide Description Antibody concentrations were expressed as Geometric Mean Titers (GMTs).
Time Frame At Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
ATP cohort for analysis of immunogenicity post dose 1: all eligible subjects with pre- & post-dose 1 serology results & were below assay cut-off for at least 1 vaccine antigen for MMR at pre-vaccination, did not meet elimination criteria up to Day 42 blood sample & complied with post-dose 1 blood sample schedule.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1252 1265 1287
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
9.8
(9.0 to 10.6)
10.7
(9.9 to 11.5)
16.3
(15.1 to 17.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Min Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Min vaccine compared to COM_MMR vaccine in terms of GMCs for anti-mumps antibodies at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% CI on the group ratio of GMCs (Inv_MMR_Min over pooled Com_MMR) should to be ≥ 0.67 for antibodies to mumps virus when tested with PRNT.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments 97.5% CI for GMC ratio was computed using ANOVA model on the log-transformed titers with vaccine group and the country as fixed effects.
Method of Estimation Estimation Parameter Adjusted GMT ratio
Estimated Value 0.60
Confidence Interval (2-Sided) 97.5%
0.53 to 0.68
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Med Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Med vaccine compared to COM_MMR vaccine in terms of GMCs for anti-mumps antibodies at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% CI on the group ratio of GMCs (Inv_MMR_Med over pooled Com_MMR) should to be ≥ 0.67 for antibodies to mumps virus when tested with PRNT.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments 97.5% CI for GMC ratio was computed using ANOVA model on the log-transformed titers with vaccine group and the country as fixed effects.
Method of Estimation Estimation Parameter Adjusted GMT ratio
Estimated Value 0.65
Confidence Interval (2-Sided) 97.5%
0.57 to 0.74
Estimation Comments [Not Specified]
8.Primary Outcome
Title Anti-rubella Virus Antibody Concentrations (by ELISA)
Hide Description Antibody concentrations were expressed as GMCs in IU/mL.
Time Frame At Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
ATP cohort for analysis of immunogenicity post dose 1: all eligible subjects with pre- & post-dose 1 serology results & were below assay cut-off for at least 1 vaccine antigen for MMR at pre-vaccination, did not meet elimination criteria up to Day 42 blood sample & complied with post-dose 1 blood sample schedule.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1359 1366 1376
Geometric Mean (97.5% Confidence Interval)
Unit of Measure: IU/mL
57.0
(54.1 to 60.0)
56.9
(54.2 to 59.8)
64.4
(61.4 to 67.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Min Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Min vaccine compared to COM_MMR vaccine in terms of GMCs for anti-rubella antibodies at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% CI on the group ratio of GMCs (Inv_MMR_Min over pooled Com_MMR) should to be ≥ 0.67 for antibodies to rubella virus when tested with ELISA.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments 97.5% CI for GMC ratio was computed using ANOVA model on the log-transformed concentrations with vaccine group and the country as fixed effects.
Method of Estimation Estimation Parameter Adjusted GMC ratio
Estimated Value 0.89
Confidence Interval (2-Sided) 97.5%
0.83 to 0.95
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inv_MMR_Med Group, Com_MMR Group
Comments Non-inferiority of Inv_MMR_Med vaccine compared to COM_MMR vaccine in terms of GMCs for anti-rubella antibodies at Day 42.
Type of Statistical Test Non-Inferiority
Comments The lower limit of the 2-sided 97.5% CI on the group ratio of GMCs (Inv_MMR_Med over pooled Com_MMR) should to be ≥ 0.67 for antibodies to rubella virus when tested with ELISA.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments 97.5% CI for GMC ratio was computed using ANOVA model on the log-transformed concentrations with vaccine group and the country as fixed effects.
Method of Estimation Estimation Parameter Adjusted GMC ratio
Estimated Value 0.88
Confidence Interval (2-Sided) 97.5%
0.83 to 0.95
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
Hide Description For measles virus, a seroresponse was defined as post-vaccination anti-measles virus antibody concentration ≥ 200 mIU/mL (ELISA) among subjects who were seronegative (antibody concentration < 150 mIU/mL) before dose 1.
Time Frame At Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
ATP cohort for analysis of immunogenicity post dose 2: all eligible subjects from US sub-cohort who received 2 doses of Inv_MMR/Com_MMR vaccine, with pre- & post-dose 2 serology results for at least 1 vaccine antigen for MMR, did not meet elimination criteria up to Day 84 blood sample & complied with post-dose 2 blood sample schedule.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 245 258 257
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of subjects
≥ 150 mIU/mL
99.6
(97.7 to 100)
98.8
(96.6 to 99.8)
98.8
(96.6 to 99.8)
≥ 200 mIU/mL
99.6
(97.7 to 100)
98.4
(96.1 to 99.6)
98.4
(96.1 to 99.6)
10.Secondary Outcome
Title Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
Hide Description For mumps virus, a seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 10 EU/mL (ELISA) among subjects who were seronegative (antibody concentration < 5 EU/mL) before dose 1.
Time Frame At Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
ATP cohort for analysis of immunogenicity post dose 2: all eligible subjects from US sub-cohort who received 2 doses of Inv_MMR/Com_MMR vaccine, with pre- & post-dose 2 serology results for at least 1 vaccine antigen for MMR, did not meet elimination criteria up to Day 84 blood sample & complied with post-dose 2 blood sample schedule.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 216 199 212
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of subjects
≥ 5 EU/mL
99.1
(96.7 to 99.9)
100
(98.2 to 100)
99.1
(96.6 to 99.9)
≥ 10 EU/mL
99.1
(96.7 to 99.9)
100
(98.2 to 100)
98.6
(95.9 to 99.7)
11.Secondary Outcome
Title Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
Hide Description For rubella virus, a seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥ 10 IU/mL (ELISA) among subjects who were seronegative (antibody concentration < 4 IU/mL) before dose 1.
Time Frame At Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
ATP cohort for analysis of immunogenicity post dose 2: all eligible subjects from US sub-cohort who received 2 doses of Inv_MMR/Com_MMR vaccine, with pre- & post-dose 2 serology results for at least 1 vaccine antigen for MMR, did not meet elimination criteria up to Day 84 blood sample & complied with post-dose 2 blood sample schedule.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 245 259 255
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of subjects
≥ 4 IU/mL
100
(98.5 to 100)
100
(98.6 to 100)
100
(98.6 to 100)
≥ 10 IU/mL
99.6
(97.7 to 100)
99.6
(97.9 to 100)
99.6
(97.8 to 100)
12.Secondary Outcome
Title Anti-measles Virus Antibody Concentrations (by ELISA)
Hide Description Antibody concentrations were expressed as GMCs in mIU/mL.
Time Frame At Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
ATP cohort for analysis of immunogenicity post dose 2: all eligible subjects from US sub-cohort who received 2 doses of Inv_MMR/Com_MMR vaccine, with pre- & post-dose 2 serology results for at least 1 vaccine antigen for MMR, did not meet elimination criteria up to Day 84 blood sample & complied with post-dose 2 blood sample schedule.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 245 258 257
Geometric Mean (95% Confidence Interval)
Unit of Measure: mIU/mL
4803.5
(4290.4 to 5378.0)
4557.7
(4061.5 to 5114.4)
4453.9
(3951.9 to 5019.8)
13.Secondary Outcome
Title Anti-mumps Virus Antibody Concentrations (by ELISA)
Hide Description Antibody concentrations were expressed as GMCs in EU/mL.
Time Frame At Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
ATP cohort for analysis of immunogenicity post dose 2: all eligible subjects from US sub-cohort who received 2 doses of Inv_MMR/Com_MMR vaccine, with pre- & post-dose 2 serology results for at least 1 vaccine antigen for MMR, did not meet elimination criteria up to Day 84 blood sample & complied with post-dose 2 blood sample schedule.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 216 199 212
Geometric Mean (95% Confidence Interval)
Unit of Measure: EU/mL
88.9
(80.4 to 98.3)
94.1
(85.3 to 103.8)
86.4
(77.4 to 96.5)
14.Secondary Outcome
Title Anti-rubella Virus Antibody Concentrations (by ELISA)
Hide Description Antibody concentrations were expressed as GMCs in IU/mL.
Time Frame At Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
ATP cohort for analysis of immunogenicity post dose 2: all eligible subjects from US sub-cohort who received 2 doses of Inv_MMR/Com_MMR vaccine, with pre- & post-dose 2 serology results for at least 1 vaccine antigen for MMR, did not meet elimination criteria up to Day 84 blood sample & complied with post-dose 2 blood sample schedule.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 245 259 255
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU/mL
112.7
(104.1 to 122.0)
110.7
(102.9 to 119.1)
110.9
(101.8 to 120.8)
15.Secondary Outcome
Title Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1
Hide Description Assessed solicited local AEs were pain, redness and swelling. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
Time Frame During the 4-day (Days 0-3) post-vaccination period
Hide Outcome Measure Data
Hide Analysis Population Description
Total Vaccinated cohort (TVC) included all vaccinated subjects with at least one vaccine administration of either Inv_MMR lots or Com_MMR lots documented.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1453 1464 1482
Measure Type: Count of Participants
Unit of Measure: Participants
Any pain
261
  18.0%
262
  17.9%
301
  20.3%
Any redness
232
  16.0%
256
  17.5%
286
  19.3%
Any swelling
89
   6.1%
97
   6.6%
122
   8.2%
16.Secondary Outcome
Title Number of Subjects With Any Solicited Local AEs Post Dose 2
Hide Description Assessed solicited local AEs were pain, redness and swelling. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
Time Frame During the 4-day (Days 0-3) post-vaccination period
Hide Outcome Measure Data
Hide Analysis Population Description
TVC included all vaccinated subjects with at least one vaccine administration of either Inv_MMR lots or Com_MMR lots documented.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1427 1440 1456
Measure Type: Count of Participants
Unit of Measure: Participants
Any pain
170
  11.9%
183
  12.7%
196
  13.5%
Any redness
159
  11.1%
196
  13.6%
217
  14.9%
Any swelling
67
   4.7%
91
   6.3%
96
   6.6%
17.Secondary Outcome
Title Number of Subjects With Any Solicited General AEs Post Dose 1
Hide Description Assessed solicited general AEs were drowsiness, irritability/fussiness and loss of appetite. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
Time Frame During the 15-day (Days 0-14) post-vaccination period
Hide Outcome Measure Data
Hide Analysis Population Description
TVC included all vaccinated subjects with at least one vaccine administration of either Inv_MMR lots or Com_MMR lots documented.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1454 1466 1486
Measure Type: Count of Participants
Unit of Measure: Participants
Any drowsiness
551
  37.9%
565
  38.5%
582
  39.2%
Any irritability / fussiness
749
  51.5%
792
  54.0%
788
  53.0%
Any loss of appetite
570
  39.2%
589
  40.2%
591
  39.8%
18.Secondary Outcome
Title Number of Subjects Reporting Any Fever Post Dose 1
Hide Description Any fever = Fever (axillary) ≥ 38°C.
Time Frame During the 43-day (Days 0-42) post-vaccination period
Hide Outcome Measure Data
Hide Analysis Population Description
TVC included all vaccinated subjects with at least one vaccine administration of either Inv_MMR lots or Com_MMR lots documented.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1454 1466 1486
Measure Type: Count of Participants
Unit of Measure: Participants
582
  40.0%
617
  42.1%
618
  41.6%
19.Secondary Outcome
Title Number of Subjects Reporting Any Fever Post Dose 2
Hide Description Any fever = Fever (axillary) ≥ 38°C.
Time Frame During the 43-day (Days 0-42) post-vaccination period
Hide Outcome Measure Data
Hide Analysis Population Description
TVC included all vaccinated subjects with at least one vaccine administration of either Inv_MMR lots or Com_MMR lots documented.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1426 1443 1455
Measure Type: Count of Participants
Unit of Measure: Participants
458
  32.1%
471
  32.6%
499
  34.3%
20.Secondary Outcome
Title Number of Subjects Reporting Any Rash Post Dose 1
Hide Description Assessed were any localized or generalized rash, rash with fever, varicella-like rash and measles/rubella-like rash. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
Time Frame During the 43-day (Days 0-42) post-vaccination period
Hide Outcome Measure Data
Hide Analysis Population Description
TVC included all vaccinated subjects with at least one vaccine administration of either Inv_MMR lots or Com_MMR lots documented.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1454 1466 1486
Measure Type: Count of Participants
Unit of Measure: Participants
Any localized or generalized
328
  22.6%
322
  22.0%
333
  22.4%
Any with fever
115
   7.9%
133
   9.1%
131
   8.8%
Any varicella like
57
   3.9%
53
   3.6%
45
   3.0%
Any measles/rubella like
53
   3.6%
61
   4.2%
68
   4.6%
21.Secondary Outcome
Title Number of Subjects Reporting Any Rash Post Dose 2
Hide Description Assessed were any localized or generalized rash, rash with fever, varicella-like rash and measles/rubella-like rash. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
Time Frame During the 43-day (Days 0-42) post-vaccination period
Hide Outcome Measure Data
Hide Analysis Population Description
TVC included all vaccinated subjects with at least one vaccine administration of either Inv_MMR lots or Com_MMR lots documented.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1426 1443 1455
Measure Type: Count of Participants
Unit of Measure: Participants
Any localized or generalized
129
   9.0%
150
  10.4%
141
   9.7%
Any with fever
52
   3.6%
63
   4.4%
53
   3.6%
Any varicella like
0
   0.0%
0
   0.0%
1
   0.1%
Any measles/rubella like
22
   1.5%
14
   1.0%
14
   1.0%
22.Secondary Outcome
Title Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 1
Hide Description Assessed MMR specific solicited general AEs were any suspected signs of meningism including febrile convulsions and parotid/salivary gland swelling. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
Time Frame During the 43-day (Days 0-42) post-vaccination period
Hide Outcome Measure Data
Hide Analysis Population Description
TVC included all vaccinated subjects with at least one vaccine administration of either Inv_MMR lots or Com_MMR lots documented.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1454 1466 1486
Measure Type: Count of Participants
Unit of Measure: Participants
Any parotid gland swelling
3
   0.2%
2
   0.1%
3
   0.2%
Any febrile convulsion
3
   0.2%
4
   0.3%
3
   0.2%
23.Secondary Outcome
Title Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 2
Hide Description Assessed MMR specific solicited general AEs were any suspected signs of meningism including febrile convulsions and parotid/salivary gland swelling. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
Time Frame During the 43-day (Days 0-42) post-vaccination period
Hide Outcome Measure Data
Hide Analysis Population Description
TVC included all vaccinated subjects with at least one vaccine administration of either Inv_MMR lots or Com_MMR lots documented.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1426 1443 1455
Measure Type: Count of Participants
Unit of Measure: Participants
Any parotid gland swelling
1
   0.1%
2
   0.1%
0
   0.0%
Any febrile convulsion
2
   0.1%
6
   0.4%
4
   0.3%
24.Secondary Outcome
Title Number of Subjects Reporting Any Unsolicited AES Post Dose 1
Hide Description Unsolicited AE was defined as any AE reported in reported in addition to those solicited during the clinical study and any solicited AE with onset outside the specified period of follow-up for solicited AEs. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
Time Frame During the 43-day (Days 0-42) post-vaccination period
Hide Outcome Measure Data
Hide Analysis Population Description
TVC included all vaccinated subjects with at least one vaccine administration of either Inv_MMR lots or Com_MMR lots documented.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1493 1497 1526
Measure Type: Count of Participants
Unit of Measure: Participants
762
  51.0%
794
  53.0%
777
  50.9%
25.Secondary Outcome
Title Number of Subjects Reporting Any Unsolicited AES Post Dose 2
Hide Description Unsolicited AE was defined as any AE reported in reported in addition to those solicited during the clinical study and any solicited AE with onset outside the specified period of follow-up for solicited AEs. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.
Time Frame During the 43-day (Days 0-42) post-vaccination period
Hide Outcome Measure Data
Hide Analysis Population Description
TVC included all vaccinated subjects with at least one vaccine administration of either Inv_MMR lots or Com_MMR lots documented.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1449 1464 1483
Measure Type: Count of Participants
Unit of Measure: Participants
667
  46.0%
703
  48.0%
690
  46.5%
26.Secondary Outcome
Title Number of Subjects Reporting Any AEs of Specific Interest
Hide Description AEs of specific interest included new onset chronic disease (NOCD) (e.g., autoimmune disorders, asthma, type I diabetes, vasculitis, celiac disease, conditions associated with sub-acute or chronic thrombocytopenia and allergies) and AEs prompting emergency room (ER) visits.
Time Frame From Day 0 through the end of the study (Day 222)
Hide Outcome Measure Data
Hide Analysis Population Description
TVC included all vaccinated subjects with at least one vaccine administration of either Inv_MMR lots or Com_MMR lots documented.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1493 1497 1526
Measure Type: Count of Participants
Unit of Measure: Participants
Any NOCD
35
   2.3%
39
   2.6%
33
   2.2%
Any AE prompting ER visit
348
  23.3%
361
  24.1%
347
  22.7%
27.Secondary Outcome
Title Number of Subjects Reporting Any Serious Adverse Events (SAEs)
Hide Description SAEs assessed include any untoward medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity.
Time Frame From Day 0 through the end of the study (Day 222)
Hide Outcome Measure Data
Hide Analysis Population Description
TVC included all vaccinated subjects with at least one vaccine administration of either Inv_MMR lots or Com_MMR lots documented.
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description:
Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
Overall Number of Participants Analyzed 1493 1497 1526
Measure Type: Count of Participants
Unit of Measure: Participants
91
   6.1%
102
   6.8%
92
   6.0%
Time Frame Solicited local & general AEs: During the 4-day (Days 0-3) and 15-day (Days 0-14) post-vaccination period, respectively; Unsolicited AEs: During the 43-day (Days 0-42) post-vaccination period; SAEs: From Day 0 through the end of the study (Day 222).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Hide Arm/Group Description Subjects received one dose of Inv_MMR, from a minimum potency lot (Inv_MMR_Min), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively. Subjects received one dose of Inv_MMR, from a mid-range or medium potency lot (Inv_MMR_Med), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose from a separate lot of the Inv_MMR vaccine (Inv_MMR_Release), for the second dose. Inv_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively. Subjects received one dose of Com_MMR vaccine (Lot 1 or Lot 2), co-administered with VV and HAV vaccines at Day 0. All US subjects were also co-administered PCV-13 vaccine. Approximately 6 weeks later, at Day 42, subjects were administered a dose of Com_MMR vaccine (Lot 1 or Lot 2), for the second dose. Com_MMR and VV vaccines were administered subcutaneously in the triceps region of the left and right arm, respectively. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.
All-Cause Mortality
Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/1493 (0.07%)      0/1497 (0.00%)      1/1526 (0.07%)    
Show Serious Adverse Events Hide Serious Adverse Events
Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   91/1493 (6.10%)      102/1497 (6.81%)      92/1526 (6.03%)    
Blood and lymphatic system disorders       
Anaemia  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Haemolytic anaemia  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Hypochromic anaemia  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Iron deficiency anaemia  1  0/1493 (0.00%)  0 3/1497 (0.20%)  3 2/1526 (0.13%)  2
Leukopenia  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Neutropenia  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Thrombocytopenia  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Cardiac disorders       
Supraventricular tachycardia  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Gastrointestinal disorders       
Anal fistula  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Constipation  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Diarrhoea  1  0/1493 (0.00%)  0 3/1497 (0.20%)  3 4/1526 (0.26%)  4
Food poisoning  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Gastritis  1  3/1493 (0.20%)  3 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Inguinal hernia  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Intestinal haemorrhage  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Perianal erythema  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Teething  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Vomiting  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 1/1526 (0.07%)  1
General disorders       
Drowning  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Influenza like illness  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Pyrexia  1  1/1493 (0.07%)  1 4/1497 (0.27%)  4 1/1526 (0.07%)  1
Hepatobiliary disorders       
Liver disorder  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Immune system disorders       
Allergy to arthropod bite  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Infections and infestations       
Adenovirus infection  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Anal abscess  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Atypical pneumonia  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Bacteraemia  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Bronchiolitis  1  6/1493 (0.40%)  6 7/1497 (0.47%)  7 2/1526 (0.13%)  2
Bronchitis  1  4/1493 (0.27%)  5 10/1497 (0.67%)  10 8/1526 (0.52%)  8
Bronchitis viral  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Campylobacter gastroenteritis  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Cellulitis  1  1/1493 (0.07%)  1 2/1497 (0.13%)  2 2/1526 (0.13%)  2
Cellulitis orbital  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Clostridium difficile colitis  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Conjunctivitis  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Croup infectious  1  2/1493 (0.13%)  2 3/1497 (0.20%)  3 4/1526 (0.26%)  4
Cystitis klebsiella  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Dengue fever  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Diarrhoea infectious  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 3/1526 (0.20%)  3
Ear infection  1  2/1493 (0.13%)  2 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Empyema  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Encephalitis  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Encephalitis brain stem  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Enterococcal bacteraemia  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Escherichia urinary tract infection  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Exanthema subitum  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Gastroenteritis  1  16/1493 (1.07%)  16 19/1497 (1.27%)  19 10/1526 (0.66%)  10
Gastroenteritis bacterial  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Gastroenteritis rotavirus  1  6/1493 (0.40%)  6 3/1497 (0.20%)  3 7/1526 (0.46%)  7
Gastroenteritis salmonella  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 2/1526 (0.13%)  2
Gastroenteritis viral  1  2/1493 (0.13%)  2 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Hand-foot-and-mouth disease  1  2/1493 (0.13%)  2 2/1497 (0.13%)  2 4/1526 (0.26%)  4
Herpangina  1  2/1493 (0.13%)  2 1/1497 (0.07%)  1 3/1526 (0.20%)  3
Influenza  1  3/1493 (0.20%)  3 2/1497 (0.13%)  2 2/1526 (0.13%)  2
Laryngitis  1  2/1493 (0.13%)  2 1/1497 (0.07%)  1 4/1526 (0.26%)  4
Laryngotracheitis obstructive  1  1/1493 (0.07%)  2 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Lower respiratory tract infection  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Meningitis  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Nail bed infection  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Nasopharyngitis  1  2/1493 (0.13%)  2 3/1497 (0.20%)  3 1/1526 (0.07%)  1
Nosocomial infection  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Otitis media  1  3/1493 (0.20%)  4 3/1497 (0.20%)  3 2/1526 (0.13%)  2
Otitis media acute  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Otitis media viral  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Otosalpingitis  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Periorbital cellulitis  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Pharyngitis  1  3/1493 (0.20%)  3 2/1497 (0.13%)  2 0/1526 (0.00%)  0
Pharyngotonsillitis  1  2/1493 (0.13%)  2 5/1497 (0.33%)  5 1/1526 (0.07%)  1
Pneumonia  1  7/1493 (0.47%)  7 14/1497 (0.94%)  14 10/1526 (0.66%)  10
Pneumonia bacterial  1  1/1493 (0.07%)  1 2/1497 (0.13%)  2 1/1526 (0.07%)  1
Pneumonia respiratory syncytial viral  1  3/1493 (0.20%)  3 1/1497 (0.07%)  1 2/1526 (0.13%)  2
Pneumonia viral  1  2/1493 (0.13%)  2 6/1497 (0.40%)  7 1/1526 (0.07%)  1
Pyelonephritis  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Pyelonephritis acute  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Respiratory syncytial virus bronchiolitis  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Respiratory syncytial virus bronchitis  1  0/1493 (0.00%)  0 2/1497 (0.13%)  2 1/1526 (0.07%)  1
Respiratory syncytial virus infection  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Rhinitis  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Sepsis  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Sinusitis  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Skin candida  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Staphylococcal bacteraemia  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Staphylococcal infection  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Subcutaneous abscess  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Tonsillitis  1  2/1493 (0.13%)  2 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Upper respiratory tract infection  1  2/1493 (0.13%)  2 3/1497 (0.20%)  3 3/1526 (0.20%)  3
Urinary tract infection  1  2/1493 (0.13%)  2 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Viral infection  1  3/1493 (0.20%)  3 1/1497 (0.07%)  1 2/1526 (0.13%)  2
Viral pharyngitis  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Viral tonsillitis  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Viral upper respiratory tract infection  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Wound infection  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Injury, poisoning and procedural complications       
Accidental poisoning  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Burns second degree  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Chest injury  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Child maltreatment syndrome  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Concussion  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Contusion  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Face injury  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Femur fracture  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Foreign body  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Head injury  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Joint dislocation  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Laceration  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Limb crushing injury  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Mouth injury  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Multiple injuries  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Poisoning  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Thermal burn  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 3/1526 (0.20%)  3
Toxicity to various agents  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Metabolism and nutrition disorders       
Dehydration  1  4/1493 (0.27%)  5 7/1497 (0.47%)  7 6/1526 (0.39%)  6
Electrolyte imbalance  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Metabolic acidosis  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 2/1526 (0.13%)  2
Type 1 diabetes mellitus  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Musculoskeletal and connective tissue disorders       
Juvenile idiopathic arthritis  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Synovitis  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Nervous system disorders       
Burning sensation  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Epilepsy  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Febrile convulsion  1  7/1493 (0.47%)  8 13/1497 (0.87%)  15 8/1526 (0.52%)  8
Intracranial pressure increased  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Seizure  1  2/1493 (0.13%)  2 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Respiratory, thoracic and mediastinal disorders       
Apnoea  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Aspiration  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Asthma  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Atelectasis  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Bronchial hyperreactivity  1  0/1493 (0.00%)  0 1/1497 (0.07%)  2 1/1526 (0.07%)  1
Bronchospasm  1  2/1493 (0.13%)  2 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Respiratory distress  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Wheezing  1  1/1493 (0.07%)  2 1/1497 (0.07%)  2 0/1526 (0.00%)  0
Skin and subcutaneous tissue disorders       
Angioedema  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Henoch-schonlein purpura  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Petechiae  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Rash  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Rash maculo-papular  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Stevens-johnson syndrome  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Toxic skin eruption  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Urticaria  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Vascular disorders       
Circulatory collapse  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Phlebitis superficial  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Thrombophlebitis  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Inv_MMR_Min Group Inv_MMR_Med Group Com_MMR Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1299/1493 (87.01%)      1311/1497 (87.58%)      1330/1526 (87.16%)    
Blood and lymphatic system disorders       
Anaemia  1  6/1493 (0.40%)  6 5/1497 (0.33%)  5 4/1526 (0.26%)  4
Hypochromic anaemia  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Iron deficiency anaemia  1  0/1493 (0.00%)  0 3/1497 (0.20%)  3 1/1526 (0.07%)  1
Lymphadenitis  1  2/1493 (0.13%)  2 2/1497 (0.13%)  2 2/1526 (0.13%)  2
Lymphadenopathy  1  8/1493 (0.54%)  8 5/1497 (0.33%)  5 2/1526 (0.13%)  2
Thrombocytosis  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Cardiac disorders       
Arrhythmia  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Congenital, familial and genetic disorders       
Dermoid cyst  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Inborn error of metabolism  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Keratosis follicular  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Naevus flammeus  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Phimosis  1  0/1493 (0.00%)  0 2/1497 (0.13%)  2 1/1526 (0.07%)  1
Talipes  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Ear and labyrinth disorders       
Cerumen impaction  1  2/1493 (0.13%)  2 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Ear disorder  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Ear pain  1  6/1493 (0.40%)  6 7/1497 (0.47%)  7 6/1526 (0.39%)  6
Middle ear inflammation  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Otorrhoea  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 3/1526 (0.20%)  4
Tympanic membrane perforation  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 2/1526 (0.13%)  2
Eye disorders       
Blepharitis  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Conjunctival hyperaemia  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Conjunctivitis allergic  1  0/1493 (0.00%)  0 2/1497 (0.13%)  3 0/1526 (0.00%)  0
Eye discharge  1  1/1493 (0.07%)  1 2/1497 (0.13%)  2 3/1526 (0.20%)  3
Eye oedema  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Eye swelling  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Eyelid bleeding  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Eyelid cyst  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Eyelid oedema  1  0/1493 (0.00%)  0 2/1497 (0.13%)  2 0/1526 (0.00%)  0
Keratitis  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Lacrimation increased  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Ocular hyperaemia  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Gastrointestinal disorders       
Abdominal discomfort  1  0/1493 (0.00%)  0 2/1497 (0.13%)  2 0/1526 (0.00%)  0
Abdominal distension  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Abdominal pain  1  3/1493 (0.20%)  3 2/1497 (0.13%)  3 3/1526 (0.20%)  3
Abdominal pain upper  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Anal fissure  1  3/1493 (0.20%)  3 3/1497 (0.20%)  3 3/1526 (0.20%)  3
Aphthous ulcer  1  6/1493 (0.40%)  6 7/1497 (0.47%)  7 3/1526 (0.20%)  3
Cheilitis  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Colitis  1  0/1493 (0.00%)  0 2/1497 (0.13%)  2 0/1526 (0.00%)  0
Constipation  1  11/1493 (0.74%)  11 11/1497 (0.73%)  13 6/1526 (0.39%)  6
Diarrhoea  1  73/1493 (4.89%)  83 71/1497 (4.74%)  76 75/1526 (4.91%)  80
Dyspepsia  1  0/1493 (0.00%)  0 2/1497 (0.13%)  2 1/1526 (0.07%)  1
Enteritis  1  19/1493 (1.27%)  19 21/1497 (1.40%)  23 19/1526 (1.25%)  20
Enterocolitis  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Faeces discoloured  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Flatulence  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Food poisoning  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Functional gastrointestinal disorder  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Gastritis  1  2/1493 (0.13%)  2 0/1497 (0.00%)  0 3/1526 (0.20%)  3
Gastrooesophageal reflux disease  1  2/1493 (0.13%)  2 2/1497 (0.13%)  2 2/1526 (0.13%)  2
Gingival disorder  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Gingival pain  1  4/1493 (0.27%)  5 4/1497 (0.27%)  4 2/1526 (0.13%)  2
Glossodynia  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Haematochezia  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 2/1526 (0.13%)  3
Haemorrhoids  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Inguinal hernia  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Lip disorder  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Lip ulceration  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Malocclusion  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Mouth ulceration  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 2/1526 (0.13%)  2
Nausea  1  1/1493 (0.07%)  1 2/1497 (0.13%)  2 2/1526 (0.13%)  2
Noninfective gingivitis  1  1/1493 (0.07%)  2 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Oral disorder  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Palatal ulcer  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Periodontal disease  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Protein-losing gastroenteropathy  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Regurgitation  1  2/1493 (0.13%)  2 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Salivary gland enlargement  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Salivary hypersecretion  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Stomatitis  1  3/1493 (0.20%)  3 6/1497 (0.40%)  6 3/1526 (0.20%)  3
Teething  1  62/1493 (4.15%)  86 71/1497 (4.74%)  104 64/1526 (4.19%)  82
Tongue blistering  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Tooth discolouration  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Tooth disorder  1  3/1493 (0.20%)  4 2/1497 (0.13%)  2 0/1526 (0.00%)  0
Toothache  1  22/1493 (1.47%)  31 17/1497 (1.14%)  21 17/1526 (1.11%)  22
Vomiting  1  43/1493 (2.88%)  55 42/1497 (2.81%)  45 48/1526 (3.15%)  51
General disorders       
Adverse drug reaction  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Application site erythema  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 2/1526 (0.13%)  2
Application site hypersensitivity  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Crying  1  4/1493 (0.27%)  5 4/1497 (0.27%)  4 5/1526 (0.33%)  7
Decreased activity  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Discomfort  1  0/1493 (0.00%)  0 2/1497 (0.13%)  2 0/1526 (0.00%)  0
Fatigue  1  2/1493 (0.13%)  2 2/1497 (0.13%)  3 1/1526 (0.07%)  1
Feeling hot  1  2/1493 (0.13%)  2 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Gait disturbance  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Influenza like illness  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Injection site bruising  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 2/1526 (0.13%)  3
Injection site erythema  1  11/1493 (0.74%)  11 15/1497 (1.00%)  15 9/1526 (0.59%)  9
Injection site haematoma  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 3/1526 (0.20%)  3
Injection site haemorrhage  1  0/1493 (0.00%)  0 3/1497 (0.20%)  3 0/1526 (0.00%)  0
Injection site induration  1  2/1493 (0.13%)  2 4/1497 (0.27%)  4 2/1526 (0.13%)  2
Injection site inflammation  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Injection site mass  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Injection site nodule  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Injection site pain  1  2/1493 (0.13%)  2 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Injection site papule  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Injection site reaction  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Injection site swelling  1  3/1493 (0.20%)  3 5/1497 (0.33%)  5 2/1526 (0.13%)  2
Injection site urticaria  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Local swelling  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Malaise  1  3/1493 (0.20%)  3 2/1497 (0.13%)  3 2/1526 (0.13%)  4
Mass  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Pain  1  334/1493 (22.37%)  431 336/1497 (22.44%)  445 378/1526 (24.77%)  500
Peripheral swelling  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Pyrexia  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Swelling  1  123/1493 (8.24%)  156 152/1497 (10.15%)  188 170/1526 (11.14%)  218
Vaccination site erythema  1  7/1493 (0.47%)  7 6/1497 (0.40%)  6 8/1526 (0.52%)  8
Vaccination site haematoma  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Vaccination site pain  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Vaccination site rash  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Vaccination site reaction  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Vaccination site swelling  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Vessel puncture site haemorrhage  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Immune system disorders       
Allergy to animal  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Drug hypersensitivity  1  1/1493 (0.07%)  1 2/1497 (0.13%)  2 3/1526 (0.20%)  3
Food allergy  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Hypersensitivity  1  2/1493 (0.13%)  2 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Milk allergy  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Multiple allergies  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Seasonal allergy  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Infections and infestations       
Abscess  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 2/1526 (0.13%)  2
Acarodermatitis  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Acute sinusitis  1  2/1493 (0.13%)  2 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Adenoiditis  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Adenoviral conjunctivitis  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Adenovirus infection  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Angular cheilitis  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Body tinea  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Bronchiolitis  1  18/1493 (1.21%)  22 22/1497 (1.47%)  22 21/1526 (1.38%)  22
Bronchitis  1  81/1493 (5.43%)  92 96/1497 (6.41%)  115 77/1526 (5.05%)  95
Bronchitis viral  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Bullous impetigo  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Burn infection  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Campylobacter gastroenteritis  1  0/1493 (0.00%)  0 2/1497 (0.13%)  2 2/1526 (0.13%)  2
Campylobacter infection  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Candida infection  1  6/1493 (0.40%)  7 9/1497 (0.60%)  9 7/1526 (0.46%)  7
Candida nappy rash  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Cellulitis  1  0/1493 (0.00%)  0 2/1497 (0.13%)  2 3/1526 (0.20%)  3
Conjunctivitis  1  63/1493 (4.22%)  67 79/1497 (5.28%)  90 79/1526 (5.18%)  87
Conjunctivitis bacterial  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Conjunctivitis viral  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Coxsackie viral infection  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 2/1526 (0.13%)  2
Croup infectious  1  4/1493 (0.27%)  4 11/1497 (0.73%)  11 12/1526 (0.79%)  13
Cryptosporidiosis infection  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Cystitis  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Ear infection  1  19/1493 (1.27%)  19 19/1497 (1.27%)  20 12/1526 (0.79%)  13
Eczema impetiginous  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Enterobiasis  1  0/1493 (0.00%)  0 2/1497 (0.13%)  2 0/1526 (0.00%)  0
Enterovirus infection  1  3/1493 (0.20%)  3 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Erythema infectiosum  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Exanthema subitum  1  2/1493 (0.13%)  2 5/1497 (0.33%)  5 1/1526 (0.07%)  1
Eye infection  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Folliculitis  1  3/1493 (0.20%)  3 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Fungal infection  1  2/1493 (0.13%)  2 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Fungal skin infection  1  1/1493 (0.07%)  1 3/1497 (0.20%)  3 0/1526 (0.00%)  0
Furuncle  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Gastritis viral  1  3/1493 (0.20%)  4 0/1497 (0.00%)  0 2/1526 (0.13%)  2
Gastroenteritis  1  88/1493 (5.89%)  93 95/1497 (6.35%)  107 93/1526 (6.09%)  100
Gastroenteritis norovirus  1  0/1493 (0.00%)  0 2/1497 (0.13%)  2 0/1526 (0.00%)  0
Gastroenteritis salmonella  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Gastroenteritis viral  1  7/1493 (0.47%)  7 6/1497 (0.40%)  6 9/1526 (0.59%)  9
Genital candidiasis  1  2/1493 (0.13%)  2 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Gingivitis  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 2/1526 (0.13%)  2
Hand-foot-and-mouth disease  1  10/1493 (0.67%)  10 23/1497 (1.54%)  23 10/1526 (0.66%)  11
Herpangina  1  9/1493 (0.60%)  9 8/1497 (0.53%)  8 8/1526 (0.52%)  8
Herpes virus infection  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Hordeolum  1  3/1493 (0.20%)  3 3/1497 (0.20%)  3 1/1526 (0.07%)  1
Impetigo  1  6/1493 (0.40%)  6 7/1497 (0.47%)  7 9/1526 (0.59%)  9
Infected bite  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 1/1526 (0.07%)  1
Influenza  1  7/1493 (0.47%)  8 11/1497 (0.73%)  13 10/1526 (0.66%)  10
Laryngitis  1  34/1493 (2.28%)  35 34/1497 (2.27%)  37 27/1526 (1.77%)  30
Lice infestation  1  0/1493 (0.00%)  0 4/1497 (0.27%)  4 0/1526 (0.00%)  0
Localised infection  1  2/1493 (0.13%)  2 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Lower respiratory tract infection  1  4/1493 (0.27%)  4 4/1497 (0.27%)  5 5/1526 (0.33%)  5
Lower respiratory tract infection viral  1  1/1493 (0.07%)  1 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Mastitis  1  0/1493 (0.00%)  0 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Molluscum contagiosum  1  1/1493 (0.07%)  1 0/1497 (0.00%)  0 0/1526 (0.00%)  0
Mycoplasma infection  1  5/1493 (0.33%)  5 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Nasopharyngitis  1  148/1493 (9.91%)  177 176/1497 (11.76%)  210 134/1526 (8.78%)  154
Oral candidiasis  1  7/1493 (0.47%)  7 1/1497 (0.07%)  1 8/1526 (0.52%)  8
Oral fungal infection  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Oral herpes  1  3/1493 (0.20%)  3 1/1497 (0.07%)  1 0/1526 (0.00%)  0
Orchitis  1  0/1493 (0.00%)  0 0/1497 (0.00%)  0 1/1526 (0.07%)  1
Otitis externa  1  5/1493 (0.33%)  5 3/1497 (0.20%)  3 3/1526 (0.20%)  3
Otitis media  1  95/1493 (6.36%)  120 99/1497 (6.61%)  117 116/1526 (7.60%)  143
Otitis media acute  1  46/1493 (3.08%)  55 49/1497 (3.27%)