Consistency Study of GlaxoSmithKline (GSK) Biologicals' MMR Vaccine (209762) (Priorix) Comparing Immunogenicity and Safety to Merck & Co., Inc.'s MMR Vaccine (M-M-R II), in Children 12 to 15 Months of Age

Consistency Study of GSK Biologicals' Measles-mumps-rubella (MMR) Vaccine (209762) (Priorix) Comparing Immunogenicity and Safety to Merck & Co., Inc.'s MMR Vaccine (M-M-R II), in Healthy Children 12 to 15 Months of Age

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01702428

Enrollment

5016

Registered

2012-10-08

Start date

2012-11-09

Completion date

2015-04-16

Last updated

2019-11-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rubella, Measles, Mumps

Keywords

Safety, Consistency study, Measles, mumps and rubella diseases, Healthy children, Immunogenicity

Brief summary

The purpose of this study is to evaluate consistency in terms of the immune response to three different lots of GSK Biologicals' trivalent MMR vaccine manufactured to target potencies, and compare its immunogenicity to Merck & Co., Inc.'s MMR vaccine, which is approved for use in the United States (US).

Detailed description

This study will evaluate the consistency of the immune response to three different lots of GSK Biologicals' trivalent investigational MMR vaccine (referred to as INV\_MMR vaccine, throughout this document) and compare its immunogenicity to the US standard of care comparator vaccine (M-M-R II, Merck and Co., Inc., referred to as COM\_MMR throughout this document) in children during their second year of life. The INV\_MMR vaccine will be given as one of three consistency lots manufactured to target potencies designated as INV\_MMR\_L1, INV\_MMR\_L2 and INV\_MMR\_L3. The COM\_MMR vaccine will be given as one of two lots designated COM\_MMR\_L1 and COM\_MMR\_L2 and will be analysed as pooled lots within the study. The MMR vaccine will be co-administered with Varivax (VV), Havrix (HAV) and (in the US sub-cohort only) Prevnar 13 (PCV-13) which are routinely administered to children of this age in the US.

Interventions

BIOLOGICALPriorix

Subjects receive 1 dose of MMR vaccine which is administered subcutaneously in the triceps region of the left arm.

BIOLOGICALM-M-R II

Subjects receive 1 dose of MMR vaccine which is administered subcutaneously in the triceps region of the left arm.

BIOLOGICALVarivax

Subjects receive 1 dose of VV vaccine which is administered subcutaneously in the triceps region of the right arm.

BIOLOGICALHavrix

Subjects receive 1 dose of HAV vaccine which is administered intramuscularly in the anterolateral region of the right thigh.

BIOLOGICALPrevnar 13

US subjects receive 1 dose of PCV-13 vaccine which is administered intramuscularly in the anterolateral region of the left thigh.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

TRIPLE (Subject, Caregiver, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

12 Months to 15 Months

Healthy volunteers

Yes

Inclusion criteria

* Male or female child between 12 and 15 months of age at the time of vaccination. * The investigator believes that the parent(s) or Legally Acceptable Representative(s) (LAR(s)) of the child, can, and will comply with the requirements of the protocol. * Written informed consent obtained from the parent(s)/LAR(s) of the child. * Child is in stable health as determined by investigator's clinical examination and assessment of child's medical history. For US children only: • Child that previously received a 3-dose series of Prevnar 13 only (i.e., no doses given as Prevnar/Prevenar), with the last dose at least 60 days prior to study entry.

Exclusion criteria

* Child in care. * Use of any investigational or non-registered product other than the study vaccine(s) during the period starting 30 days before the day of study vaccination (i.e., 30 days prior to Day 0) or planned use during the entire study period. * Concurrently participating in another clinical study, in which the child has been or will be exposed to an investigational or a non-investigational product. * Chronic administration of immunosuppressants, or other immune-modifying drugs during the period starting 180 days prior to the first vaccine dose or any planned administration of immunosuppressive and immune-modifying drugs during the entire study. * For corticosteroids, this will mean prednisone, ≥0.5 mg/kg/day or equivalent. * Inhaled and topical steroids are allowed. * Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting 30 days prior to study vaccination at Visit 1 and ending at Visit 2. Please Note: * Inactivated influenza (Flu) vaccine and Haemophilus influenzae type b conjugate vaccine (Hib) vaccines may be given at any time, including the day of study vaccination (Flu and Hib vaccines must be administered at a different location than the study vaccine/s). * Any other age appropriate vaccine may be given starting at Visit 2 and anytime thereafter. * Administration of immunoglobulins and/or any blood products during the period starting 180 days prior to study vaccination at Visit 1 or planned administration from the date of vaccination through the immunogenicity evaluation at Visit 2. * History of measles, mumps, rubella, varicella/zoster and/or hepatitis A disease. * Known exposure to measles, mumps, rubella and/or varicella/zoster during the period starting within 30 days prior to first study vaccination. * Previous vaccination against measles, mumps, rubella, hepatitis A and/or varicella virus. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * A family history of congenital or hereditary immunodeficiency. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, including hypersensitivity to neomycin, latex or gelatin. * Blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems. * Acute disease at the time of enrollment. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection without fever. * Active untreated tuberculosis based on medical history. * Any other condition which, in the opinion of the investigator, prevents the child from participating in the study. For US children only: * Child that previously received a vaccination with heptavalent Prevnar/Prevenar (prior vaccination should be with 3 doses of Prevnar 13 only). * Child that previously received a fourth dose of any pneumococcal conjugate vaccine.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value	At Day 42	Seroresponse was defined as post-vaccination anti-measles virus antibody concentration ≥200 milli International Unit/Milliliter (mIU/mL) among subjects who were seronegative (antibody concentration \<150 mIU/mL) before vaccination. This outcome measure is applicable to reporting groups INV\_MMR\_L1, INV\_MMR\_L2 and INV\_MMR\_L3 as analysis was performed on subjects who received one of the lots of INV\_MMR vaccine.
Anti-measles Virus Antibody Concentrations	At Day 42	Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. This outcome measure is applicable to reporting groups INV\_MMR\_L1, INV\_MMR\_L2 and INV\_MMR\_L3 as analysis was performed on subjects who received one of the lots of INV\_MMR vaccine.
Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value	At Day 42	Seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥10 ELISA Unit/Milliliter (EU/mL) among subjects who were seronegative (antibody concentrations \<5 EU/mL) before vaccination. This outcome measure is applicable to reporting groups INV\_MMR\_L1, INV\_MMR\_L2 and INV\_MMR\_L3 as analysis was performed on subjects who received one of the lots of INV\_MMR vaccine.
Anti-mumps Virus Antibody Concentration	At Day 42	Antibody concentrations were expressed as GMCs in EU/mL. This outcome measure is applicable to reporting groups INV\_MMR\_L1, INV\_MMR\_L2 and INV\_MMR\_L3 as analysis was performed on subjects who received one of the lots of INV\_MMR vaccine.
Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value	At Day 42	Seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥10 International Unit/Milliliter (IU/mL) among subjects who were seronegative (antibody concentrations \<4 IU/mL) before vaccination. This outcome measure is applicable to reporting groups INV\_MMR\_L1, INV\_MMR\_L2 and INV\_MMR\_L3 as analysis was performed on subjects who received one of the lots of INV\_MMR vaccine.
Anti-rubella Virus Antibody Concentration	At Day 42	Antibody concentrations were expressed as GMCs in IU/mL. This outcome measure is applicable to reporting groups INV\_MMR\_L1, INV\_MMR\_L2 and INV\_MMR\_L3 as analysis was performed on subjects who received one of the lots of INV\_MMR vaccine.
Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	At Day 42	Seroresponse was defined as post-vaccination anti-measles virus antibody concentration ≥200 mIU/mL among subjects who were seronegative (antibody concentration \<150 mIU/mL) before vaccination. Criteria to demonstrate an acceptable immune response for INV\_MMR in terms of seroresponse rates to measles virus at Day 42: The LL of 2-sided 95% CI for the seroresponse rate for the pooled INV\_MMR lots is ≥90% for antibodies to measles virus.
Anti-measles Virus Antibody Concentrations in Pooled MMR Groups	At Day 42	Antibody concentrations were expressed as GMCs in mIU/mL.
Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	At Day 42	Seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥10 EU/mL among subjects who were seronegative (antibody concentrations \<5 EU/mL) before vaccination.
Anti-mumps Virus Antibody Concentration in Pooled MMR Groups	At Day 42	Antibody concentrations were expressed as GMCs in EU/mL.
Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	At Day 42	Seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥10 IU/mL among subjects who were seronegative (antibody concentrations \<4 IU/mL) before vaccination. Criteria to demonstrate an acceptable immune response for INV\_MMR in terms of seroresponse rates to rubella virus at Day 42: The LL of 2-sided 95% CI for the seroresponse rate for the pooled INV\_MMR lots is ≥90% for antibodies to rubella virus.
Anti-rubella Virus Antibody Concentration in Pooled MMR Groups	At Day 42	Antibody concentrations were expressed as GMCs in IU/mL.

Secondary

Measure	Time frame	Description
Percentage of Subjects With an Anti-Varicella Zoster Virus (VZV) Antibody Concentration Equal to or Above the Cut-off Value in US Sub-cohort of Pooled MMR Groups	At Day 42	Seroresponse was defined as post-vaccination anti-VZV antibody concentration ≥75 mIU/mL among subjects who were seronegative (antibody concentration \<25 mIU/mL) before vaccination.
Anti-VZV Virus Antibody Concentration in US Sub-cohort of Pooled MMR Groups	At Day 42	Antibody concentrations were expressed as GMCs in mIU/mL.
Percentage of Subjects With an Anti-HAV Antibody Concentration Equal to or Above the Cut-off Value in US Sub-cohort of Pooled MMR Groups	At Day 42	Percentage of subjects with an Anti-HAV antibody concentration equal to or above 15 mIU/mL were reported.
Anti-HAV Antibody Concentrations in US Sub-cohort of Pooled MMR Groups	At Day 42	Antibody concentrations were expressed as GMCs in mIU/mL.
Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	At Day 42	Antibody concentrations were expressed as GMCs in microgram/Milliliter (µg/mL).
Number of Subjects With Any Solicited Local Adverse Events (AEs)	During the 4-days (Days 0-3) post-vaccination period	Assessed solicited local AEs were pain, redness and swelling. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination.
Number of Subjects With Any Solicited General AEs	During the 15-days (Days 0-14) post-vaccination period	Assessed solicited general AEs were drowsiness, irritability and loss of appetite. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination.
Number of Subjects Reporting Any Fever	During the 43-days (Days 0-42) post-vaccination period	Any fever = Fever ≥ 38°C.
Number of Subjects Reporting Any Rash	During the 43-days (Days 0-42) post-vaccination period	Assessed were any localized or generalized rash, rash with fever, varicella-like rash, measles/rubella-like rash. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination.
Number of Subjects Reporting Any MMR Specific Solicited AEs	During the 43-days (Days 0-42) post-vaccination period	Assessed MMR specific solicited AEs were any suspected signs of meningism including febrile convulsions and parotid/salivary gland swelling. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination.
Number of Subjects Reporting Any Unsolicited AEs	During the 43-days (Days 0-42) post-vaccination period	Unsolicited adverse event (AE) was defined as any adverse event reported in addition to those solicited during the clinical study and also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination.
Number of Subjects Reporting AEs of Specific Interest	From Day 0 through the end of study (Day 180)	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.
Number of Subjects Reporting Any Serious Adverse Events (SAEs)	From Day 0 through the end of study (Day 180)	SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity. Any SAE = Occurrence of SAE regardless of intensity grade or relation to vaccination.

Countries

Estonia, Finland, Mexico, Puerto Rico, Spain, United States

Participant flow

Recruitment details

13 subjects from 5016 were allocated subject number but no study vaccine was administered. Therefore, the number of subjects started is 5003.

Pre-assignment details

Sub-cohorts for this study were as follows: • US sub-cohort: Subjects recruited in US and received INV\_MMR or COM\_MMR co-administered with Varivax (VV), Havrix (HAV) and Prevnar (PCV-13) vaccines at Visit 1 (Day 0). • Non-US sub-cohort: Subjects recruited outside US and received INV\_MMR or COM\_MMR co-administered with VV and HAV vaccines at Day 0.

Participants by arm

Arm	Count
INV_MMR_L1 Group Subjects received 1 dose of INV\_MMR\_L1 vaccine co-administered with VV and HAV vaccines at Visit 1 (Day 0). All US subjects were also given PCV-13 vaccine. The MMR vaccine was administered subcutaneously in the triceps region of the left arm while the VV vaccine was administered subcutaneously in the triceps region of the right arm. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.	1,239
INV_MMR_L2 Group Subjects received 1 dose of INV\_MMR\_L2 vaccine co-administered with VV and HAV vaccines at Visit 1 (Day 0). All US subjects were also given PCV-13 vaccine. The MMR vaccine was administered subcutaneously in the triceps region of the left arm while the VV vaccine was administered subcutaneously in the triceps region of the right arm. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.	1,232
INV_MMR_L3 Group Subjects received 1 dose of INV\_MMR\_L3 vaccine co-administered with VV and HAV vaccines at Visit 1 (Day 0). All US subjects were also given PCV-13 vaccine. The MMR vaccine was administered subcutaneously in the triceps region of the left arm while the VV vaccine was administered subcutaneously in the triceps region of the right arm. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively.	1,243
COM_MMR Group Subjects received 1 dose of COM\_MMR Lot 1 and Lot 2 co-administered with VV and HAV vaccines at Visit 1 (Day 0). All US subjects were also given PCV-13 vaccine. The MMR vaccine was administered subcutaneously in the triceps region of the left arm while the VV vaccine was administered subcutaneously in the triceps region of the right arm. HAV and PCV-13 vaccines were administered intramuscularly in the anterolateral region of the right and left thigh, respectively. Pooled analysis was conducted for this group.	1,289
Total	5,003

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	2	0	0	0
Overall Study	Lost Coverage	0	0	0	1
Overall Study	Lost Health Plan	3	5	0	2
Overall Study	Lost to Follow-up	33	41	37	44
Overall Study	Mother transferred care	0	1	0	0
Overall Study	Parents cannot assist to site	1	0	1	0
Overall Study	Parents too busy	1	0	0	0
Overall Study	Protocol Violation	3	0	1	0
Overall Study	Withdrawal by Subject	21	23	14	10

Baseline characteristics

Characteristic	INV_MMR_L1 Group	Total	COM_MMR Group	INV_MMR_L3 Group	INV_MMR_L2 Group
Age, Continuous	12.3 Months STANDARD_DEVIATION 0.7	12.3 Months STANDARD_DEVIATION 0.7	12.3 Months STANDARD_DEVIATION 0.7	12.3 Months STANDARD_DEVIATION 0.7	12.3 Months STANDARD_DEVIATION 0.7
Race/Ethnicity, Customized African Heritage / African American	60 Participants	239 Participants	70 Participants	57 Participants	52 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	25 Participants	126 Participants	31 Participants	33 Participants	37 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	14 Participants	36 Participants	9 Participants	7 Participants	6 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	8 Participants	38 Participants	10 Participants	10 Participants	10 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	1 Participants	6 Participants	1 Participants	2 Participants	2 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	21 Participants	93 Participants	26 Participants	21 Participants	25 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	3 Participants	11 Participants	2 Participants	5 Participants	1 Participants
Race/Ethnicity, Customized Other	170 Participants	650 Participants	163 Participants	162 Participants	155 Participants
Race/Ethnicity, Customized White - Arabic / North African Heritage	5 Participants	20 Participants	7 Participants	2 Participants	6 Participants
Race/Ethnicity, Customized White - Caucasian / European Heritage	932 Participants	3784 Participants	970 Participants	944 Participants	938 Participants
Sex: Female, Male Female	607 Participants	2434 Participants	618 Participants	615 Participants	594 Participants
Sex: Female, Male Male	632 Participants	2569 Participants	671 Participants	628 Participants	638 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	0 / 1,239	0 / 1,232	0 / 1,243	0 / 3,714	0 / 1,289
other Total, other adverse events	1,089 / 1,239	1,053 / 1,232	1,090 / 1,243	3,232 / 3,714	1,138 / 1,289
serious Total, serious adverse events	21 / 1,239	28 / 1,232	28 / 1,243	77 / 3,714	25 / 1,289

Outcome results

Primary

Anti-measles Virus Antibody Concentrations

Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. This outcome measure is applicable to reporting groups INV\_MMR\_L1, INV\_MMR\_L2 and INV\_MMR\_L3 as analysis was performed on subjects who received one of the lots of INV\_MMR vaccine.

Time frame: At Day 42

Population: ATP cohort for immunogenicity included subjects who received at least 1 MMR vaccine, were below the assay cut-off at pre-vaccination \& with pre \& post dose serology results available for at least 1 antigen of MMR, did not meet any elimination criteria up to Visit 2 blood sample \& complied with post dose blood sample schedule

Arm	Measure	Value (GEOMETRIC_MEAN)
INV_MMR _L1 Group	Anti-measles Virus Antibody Concentrations	2970.3 mIU/mL
INV_MMR _L2 Group	Anti-measles Virus Antibody Concentrations	3023.6 mIU/mL
INV_MMR _L3 Group	Anti-measles Virus Antibody Concentrations	3058.3 mIU/mL

Comparison: Adjusted GMC ratio (INV\_MMR\_L1 Group divided by INV\_MMR\_L2 Group) for antibodies to measles virus at Day 42.95% CI: [0.91, 1.06]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L1 Group divided by INV\_MMR\_L3 Group) for antibodies to measles virus at Day 42.95% CI: [0.9, 1.05]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L2 Group divided by INV\_MMR\_L1 Group) for antibodies to measles virus at Day 42.95% CI: [0.94, 1.09]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L2 Group divided by INV\_MMR\_L3 Group) for antibodies to measles virus at Day 42.95% CI: [0.91, 1.06]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L3 Group divided by INV\_MMR\_L1 Group) for antibodies to measles virus at Day 42.95% CI: [0.95, 1.11]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L3 Group divided by INV\_MMR\_L2 Group) for antibodies to measles virus at Day 42.95% CI: [0.94, 1.09]ANOVA

Primary

Anti-measles Virus Antibody Concentrations in Pooled MMR Groups

Antibody concentrations were expressed as GMCs in mIU/mL.

Time frame: At Day 42

Arm	Measure	Value (GEOMETRIC_MEAN)
INV_MMR _L1 Group	Anti-measles Virus Antibody Concentrations in Pooled MMR Groups	3017.4 mIU/mL
INV_MMR _L2 Group	Anti-measles Virus Antibody Concentrations in Pooled MMR Groups	3074.4 mIU/mL

Comparison: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for antibodies to measles virus at Day 42.95% CI: [0.93, 1.05]ANOVA

Primary

Anti-mumps Virus Antibody Concentration

Antibody concentrations were expressed as GMCs in EU/mL. This outcome measure is applicable to reporting groups INV\_MMR\_L1, INV\_MMR\_L2 and INV\_MMR\_L3 as analysis was performed on subjects who received one of the lots of INV\_MMR vaccine.

Time frame: At Day 42

Arm	Measure	Value (GEOMETRIC_MEAN)
INV_MMR _L1 Group	Anti-mumps Virus Antibody Concentration	71.7 EU/mL
INV_MMR _L2 Group	Anti-mumps Virus Antibody Concentration	76.9 EU/mL
INV_MMR _L3 Group	Anti-mumps Virus Antibody Concentration	69.0 EU/mL

Comparison: Adjusted GMC ratio (INV\_MMR\_L1 Group divided by INV\_MMR\_L2 Group) for antibodies to mumps virus at Day 42.95% CI: [0.87, 1]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L1 Group divided by INV\_MMR\_L3 Group) for antibodies to mumps virus at Day 42.95% CI: [0.97, 1.11]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L2 Group divided by INV\_MMR\_L1 Group) for antibodies to mumps virus at Day 42.95% CI: [1, 1.15]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L2 Group divided by INV\_MMR\_L3 Group) for antibodies to mumps virus at Day 42.95% CI: [1.04, 1.19]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L3 Group divided by INV\_MMR\_L1 Group) for antibodies to mumps virus at Day 42.95% CI: [0.9, 1.03]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L3 Group divided by INV\_MMR\_L2 Group) for antibodies to mumps virus at Day 42.95% CI: [0.84, 0.96]ANOVA

Primary

Anti-mumps Virus Antibody Concentration in Pooled MMR Groups

Antibody concentrations were expressed as GMCs in EU/mL.

Time frame: At Day 42

Arm	Measure	Value (GEOMETRIC_MEAN)
INV_MMR _L1 Group	Anti-mumps Virus Antibody Concentration in Pooled MMR Groups	72.4 EU/mL
INV_MMR _L2 Group	Anti-mumps Virus Antibody Concentration in Pooled MMR Groups	69.1 EU/mL

Comparison: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for antibodies to mumps virus at Day 42.95% CI: [0.99, 1.11]ANOVA

Primary

Anti-rubella Virus Antibody Concentration

Antibody concentrations were expressed as GMCs in IU/mL. This outcome measure is applicable to reporting groups INV\_MMR\_L1, INV\_MMR\_L2 and INV\_MMR\_L3 as analysis was performed on subjects who received one of the lots of INV\_MMR vaccine.

Time frame: At Day 42

Arm	Measure	Value (GEOMETRIC_MEAN)
INV_MMR _L1 Group	Anti-rubella Virus Antibody Concentration	57.2 IU/mL
INV_MMR _L2 Group	Anti-rubella Virus Antibody Concentration	53.1 IU/mL
INV_MMR _L3 Group	Anti-rubella Virus Antibody Concentration	57.0 IU/mL

Comparison: Adjusted GMC ratio (INV\_MMR\_L1 Group divided by INV\_MMR\_L2 Group) for antibodies to rubella virus at Day 42.~.95% CI: [1.01, 1.15]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L1 Group divided by INV\_MMR\_L3 Group) for antibodies to rubella virus at Day 42.95% CI: [0.94, 1.07]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L2 Group divided by INV\_MMR\_L1 Group) for antibodies to rubella virus at Day 42.95% CI: [0.87, 0.99]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L2 Group divided by INV\_MMR\_L3 Group) for antibodies to rubella virus at Day 42.95% CI: [0.87, 0.99]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L3 Group divided by INV\_MMR\_L1 Group) for antibodies to rubella virus at Day 42.95% CI: [0.93, 1.07]ANOVA

Comparison: Adjusted GMC ratio (INV\_MMR\_L3 Group divided by INV\_MMR\_L2 Group) for antibodies to rubella virus at Day 42.95% CI: [1.01, 1.15]ANOVA

Primary

Anti-rubella Virus Antibody Concentration in Pooled MMR Groups

Antibody concentrations were expressed as GMCs in IU/mL.

Time frame: At Day 42

Arm	Measure	Value (GEOMETRIC_MEAN)
INV_MMR _L1 Group	Anti-rubella Virus Antibody Concentration in Pooled MMR Groups	55.7 IU/mL
INV_MMR _L2 Group	Anti-rubella Virus Antibody Concentration in Pooled MMR Groups	64.0 IU/mL

Comparison: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for antibodies to rubella virus at Day 42.95% CI: [0.83, 0.92]ANOVA

Primary

Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value

Seroresponse was defined as post-vaccination anti-measles virus antibody concentration ≥200 milli International Unit/Milliliter (mIU/mL) among subjects who were seronegative (antibody concentration \<150 mIU/mL) before vaccination. This outcome measure is applicable to reporting groups INV\_MMR\_L1, INV\_MMR\_L2 and INV\_MMR\_L3 as analysis was performed on subjects who received one of the lots of INV\_MMR vaccine.

Time frame: At Day 42

Population: According to protocol (ATP) cohort for immunogenicity included subjects who received at least 1 MMR vaccine, were below the assay cut-off at pre-vaccination \& with pre \& post dose serology results available for at least 1 antigen of MMR, did not meet any elimination criteria up to Visit 2 blood sample \& complied with post dose blood sample schedule

Arm	Measure	Group	Value (NUMBER)
INV_MMR _L1 Group	Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-measles ≥ 150 mIU/mL	98.2 Percentage of subjects
INV_MMR _L1 Group	Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-measles ≥ 200 mIU/mL	98.1 Percentage of subjects
INV_MMR _L2 Group	Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-measles ≥ 150 mIU/mL	98.9 Percentage of subjects
INV_MMR _L2 Group	Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-measles ≥ 200 mIU/mL	98.6 Percentage of subjects
INV_MMR _L3 Group	Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-measles ≥ 150 mIU/mL	98.1 Percentage of subjects
INV_MMR _L3 Group	Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-measles ≥ 200 mIU/mL	97.8 Percentage of subjects

Comparison: Difference between groups (INV\_MMR\_L1 Group minus INV\_MMR\_L2 Group) in percentage of subjects with anti-measles antibody concentration ≥200 mIU/mL.95% CI: [-1.69, 0.58]

Comparison: Difference between groups (INV\_MMR\_L2 Group minus INV\_MMR\_L3 Group) in percentage of subjects with anti-measles antibody concentration ≥200 mIU/mL.95% CI: [-0.35, 1.98]

Comparison: Difference between groups (INV\_MMR\_L1 Group minus INV\_MMR\_L3 Group) in percentage of subjects with anti-measles antibody concentration ≥200 mIU/mL.95% CI: [-0.98, 1.5]

Primary

Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups

Seroresponse was defined as post-vaccination anti-measles virus antibody concentration ≥200 mIU/mL among subjects who were seronegative (antibody concentration \<150 mIU/mL) before vaccination. Criteria to demonstrate an acceptable immune response for INV\_MMR in terms of seroresponse rates to measles virus at Day 42: The LL of 2-sided 95% CI for the seroresponse rate for the pooled INV\_MMR lots is ≥90% for antibodies to measles virus.

Time frame: At Day 42

Arm	Measure	Group	Value (NUMBER)
INV_MMR _L1 Group	Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Anti-measles ≥ 150 mIU/mL	98.4 Percentage of subjects
INV_MMR _L1 Group	Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Anti-measles ≥ 200 mIU/mL	98.2 Percentage of subjects
INV_MMR _L2 Group	Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Anti-measles ≥ 150 mIU/mL	98.1 Percentage of subjects
INV_MMR _L2 Group	Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Anti-measles ≥ 200 mIU/mL	98.0 Percentage of subjects

Comparison: Difference in percentage (INV\_MMR Group minus COM\_MMR Group) of subjects with anti-measles antibody concentration at Day 42.95% CI: [-0.68, 1.25]

Primary

Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value

Seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥10 ELISA Unit/Milliliter (EU/mL) among subjects who were seronegative (antibody concentrations \<5 EU/mL) before vaccination. This outcome measure is applicable to reporting groups INV\_MMR\_L1, INV\_MMR\_L2 and INV\_MMR\_L3 as analysis was performed on subjects who received one of the lots of INV\_MMR vaccine.

Time frame: At Day 42

Arm	Measure	Group	Value (NUMBER)
INV_MMR _L1 Group	Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-mumps ≥ 5 EU/mL	99.7 Percentage of subjects
INV_MMR _L1 Group	Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-mumps ≥ 10 EU/mL	98.6 Percentage of subjects
INV_MMR _L2 Group	Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-mumps ≥ 5 EU/mL	99.3 Percentage of subjects
INV_MMR _L2 Group	Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-mumps ≥ 10 EU/mL	98.6 Percentage of subjects
INV_MMR _L3 Group	Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-mumps ≥ 5 EU/mL	99.2 Percentage of subjects
INV_MMR _L3 Group	Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-mumps ≥ 10 EU/mL	98.0 Percentage of subjects

Comparison: Difference between groups (INV\_MMR\_L1 Group minus INV\_MMR\_L2 Group) in percentage of subjects with anti-mumps antibody concentration ≥10 EU/mL.95% CI: [-1.05, 1.09]

Comparison: Difference between groups (INV\_MMR\_L1 Group minus INV\_MMR\_L3 Group) in percentage of subjects with anti-mumps antibody concentration ≥10 EU/mL.95% CI: [-0.5, 1.81]

Comparison: Difference between groups (INV\_MMR\_L2 Group minus INV\_MMR\_L3 Group) in percentage of subjects with anti-mumps antibody concentration ≥10 EU/mL.95% CI: [-0.53, 1.79]

Primary

Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups

Seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥10 EU/mL among subjects who were seronegative (antibody concentrations \<5 EU/mL) before vaccination.

Time frame: At Day 42

Arm	Measure	Group	Value (NUMBER)
INV_MMR _L1 Group	Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Anti-mumps ≥ 5 EU/mL	99.4 Percentage of subjects
INV_MMR _L1 Group	Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Anti-mumps ≥ 10 EU/mL	98.4 Percentage of subjects
INV_MMR _L2 Group	Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Anti-mumps ≥ 5 EU/mL	99.3 Percentage of subjects
INV_MMR _L2 Group	Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Anti-mumps ≥ 10 EU/mL	97.6 Percentage of subjects

Comparison: Difference in percentage (INV\_MMR Group minus COM\_MMR Group) of subjects with anti-mumps antibody concentration at Day 42.95% CI: [-0.1, 1.96]

Primary

Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value

Seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥10 International Unit/Milliliter (IU/mL) among subjects who were seronegative (antibody concentrations \<4 IU/mL) before vaccination. This outcome measure is applicable to reporting groups INV\_MMR\_L1, INV\_MMR\_L2 and INV\_MMR\_L3 as analysis was performed on subjects who received one of the lots of INV\_MMR vaccine.

Time frame: At Day 42

Arm	Measure	Group	Value (NUMBER)
INV_MMR _L1 Group	Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-rubella ≥ 4 IU/mL	99.4 Percentage of subjects
INV_MMR _L1 Group	Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-rubella ≥ 10 IU/mL	97.2 Percentage of subjects
INV_MMR _L2 Group	Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-rubella ≥ 4 IU/mL	99.7 Percentage of subjects
INV_MMR _L2 Group	Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-rubella ≥ 10 IU/mL	97.1 Percentage of subjects
INV_MMR _L3 Group	Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-rubella ≥ 4 IU/mL	99.4 Percentage of subjects
INV_MMR _L3 Group	Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-rubella ≥ 10 IU/mL	97.7 Percentage of subjects

Comparison: Difference between groups (INV\_MMR\_L1 Group minus INV\_MMR\_L2 Group) in percentage of subjects with anti-rubella antibody concentration ≥10 IU/mL.95% CI: [-1.3, 1.58]

Comparison: Difference between groups (INV\_MMR\_L1 Group minus INV\_MMR\_L3 Group) in percentage of subjects with anti-rubella antibody concentration ≥10 IU/mL.95% CI: [-1.86, 0.86]

Comparison: Difference between groups (INV\_MMR\_L2 Group minus INV\_MMR\_L3 Group) in percentage of subjects with anti-rubella antibody concentration ≥10 IU/mL.95% CI: [-2.02, 0.74]

Primary

Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups

Seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥10 IU/mL among subjects who were seronegative (antibody concentrations \<4 IU/mL) before vaccination. Criteria to demonstrate an acceptable immune response for INV\_MMR in terms of seroresponse rates to rubella virus at Day 42: The LL of 2-sided 95% CI for the seroresponse rate for the pooled INV\_MMR lots is ≥90% for antibodies to rubella virus.

Time frame: At Day 42

Arm	Measure	Group	Value (NUMBER)
INV_MMR _L1 Group	Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Anti-rubella ≥ 4 IU/mL	99.5 Percentage of subjects
INV_MMR _L1 Group	Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Anti-rubella ≥ 10 IU/mL	97.3 Percentage of subjects
INV_MMR _L2 Group	Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Anti-rubella ≥ 4 IU/mL	99.6 Percentage of subjects
INV_MMR _L2 Group	Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Anti-rubella ≥ 10 IU/mL	98.5 Percentage of subjects

Comparison: Difference in percentage (INV\_MMR Group minus COM\_MMR Group) of subjects with anti-rubella antibody concentration at Day 42.95% CI: [-2, -0.15]

Secondary

Anti-HAV Antibody Concentrations in US Sub-cohort of Pooled MMR Groups

Antibody concentrations were expressed as GMCs in mIU/mL.

Time frame: At Day 42

Population: ATP cohort for immunogenicity included subjects from US sub-cohort who received at least 1 MMR vaccine, were below the assay cut-off at pre-vaccination \& with pre \& post dose serology results available for at least 1 antigen of MMR, did not meet any elimination criteria up to Visit 2 blood sample \& complied with post dose blood sample schedule

Arm	Measure	Value (GEOMETRIC_MEAN)
INV_MMR _L1 Group	Anti-HAV Antibody Concentrations in US Sub-cohort of Pooled MMR Groups	42.0 mIU/mL
INV_MMR _L2 Group	Anti-HAV Antibody Concentrations in US Sub-cohort of Pooled MMR Groups	42.4 mIU/mL

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for antibodies to HAV virus at Day 42.95% CI: [0.86, 1.11]ANOVA

Secondary

Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups

Antibody concentrations were expressed as GMCs in microgram/Milliliter (µg/mL).

Time frame: At Day 42

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
INV_MMR _L1 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 4 antibody	1.618 µg/mL
INV_MMR _L1 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 9V antibody	2.318 µg/mL
INV_MMR _L1 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 6A antibody	5.840 µg/mL
INV_MMR _L1 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 14 antibody	6.578 µg/mL
INV_MMR _L1 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 3 antibody	0.506 µg/mL
INV_MMR _L1 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 18C antibody	2.102 µg/mL
INV_MMR _L1 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 6B antibody	5.872 µg/mL
INV_MMR _L1 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 19A antibody	4.731 µg/mL
INV_MMR _L1 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 5 antibody	2.106 µg/mL
INV_MMR _L1 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 19F antibody	4.251 µg/mL
INV_MMR _L1 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 7F antibody	3.691 µg/mL
INV_MMR _L1 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 23F antibody	2.198 µg/mL
INV_MMR _L1 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 1 antibody	2.257 µg/mL
INV_MMR _L2 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 23F antibody	2.291 µg/mL
INV_MMR _L2 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 1 antibody	2.425 µg/mL
INV_MMR _L2 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 3 antibody	0.496 µg/mL
INV_MMR _L2 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 4 antibody	1.872 µg/mL
INV_MMR _L2 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 5 antibody	2.280 µg/mL
INV_MMR _L2 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 6A antibody	5.743 µg/mL
INV_MMR _L2 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 6B antibody	5.838 µg/mL
INV_MMR _L2 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 7F antibody	3.814 µg/mL
INV_MMR _L2 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 9V antibody	2.282 µg/mL
INV_MMR _L2 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 14 antibody	7.053 µg/mL
INV_MMR _L2 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 18C antibody	2.217 µg/mL
INV_MMR _L2 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 19A antibody	4.821 µg/mL
INV_MMR _L2 Group	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	anti-PnPS 19F antibody	4.260 µg/mL

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for anti-PnPS 1 antibody at Day 42.95% CI: [0.85, 1.05]ANCOVA

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for anti-PnPS 3 antibody at Day 42.95% CI: [0.91, 1.08]ANCOVA

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for anti-PnPS 4 antibody at Day 42.95% CI: [0.79, 0.98]ANCOVA

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for anti-PnPS 5 antibody at Day 42.95% CI: [0.83, 1.01]ANCOVA

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for anti-PnPS 6A antibody at Day 42.95% CI: [0.92, 1.11]ANCOVA

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for anti-PnPS 6B antibody at Day 42.95% CI: [0.89, 1.09]ANCOVA

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for anti-PnPS 7F antibody at Day 42.95% CI: [0.86, 1.03]ANCOVA

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for anti-PnPS 9V antibody at Day 42.95% CI: [0.9, 1.08]ANCOVA

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for anti-PnPS 14 antibody at Day 42.95% CI: [0.81, 1.02]ANCOVA

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for anti-PnPS 18C antibody at Day 42.95% CI: [0.84, 1.02]ANCOVA

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for anti-PnPS 19A antibody at Day 42.95% CI: [0.87, 1.07]ANCOVA

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for anti-PnPS 19F antibody at Day 42.95% CI: [0.87, 1.06]ANCOVA

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for anti-PnPS 23F antibody at Day 42.95% CI: [0.85, 1.06]ANCOVA

Secondary

Anti-VZV Virus Antibody Concentration in US Sub-cohort of Pooled MMR Groups

Antibody concentrations were expressed as GMCs in mIU/mL.

Time frame: At Day 42

Arm	Measure	Value (GEOMETRIC_MEAN)
INV_MMR _L1 Group	Anti-VZV Virus Antibody Concentration in US Sub-cohort of Pooled MMR Groups	169.6 mIU/mL
INV_MMR _L2 Group	Anti-VZV Virus Antibody Concentration in US Sub-cohort of Pooled MMR Groups	167.2 mIU/mL

Comparison: In US sub-cohort: Adjusted GMC ratio (INV\_MMR Group divided by COM\_MMR Group) for antibodies to VZV virus at Day 42.95% CI: [0.95, 1.08]ANOVA

Secondary

Number of Subjects Reporting AEs of Specific Interest

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 study (Day 180)