Measles, Mumps, Rubella, Measles-Mumps-Rubella Vaccine
Conditions
Keywords
Safety, Measles, mumps and rubella diseases, Immunogenicity
Brief summary
The purpose of this study is to evaluate end of shelf-life potency in terms of the immunogenicity and safety of GSK Biologicals' trivalent MMR vaccine, by comparing it to Merck & Co., Inc.'s MMR vaccine, which is approved for use in the United States (US).
Detailed description
This trial is a Phase IIIA, randomized, observer-blind, controlled, multi-center, multi-country study with four parallel groups. This study will evaluate the immunogenicity and safety of GSK Biologicals' trivalent investigational MMR vaccine (referred to as Inv\_MMR vaccine, throughout this document) in contrast 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 first dose of this two-dose study is designed to establish the end of shelf-life potency of Inv\_MMR vaccine. The Inv\_MMR vaccine will be given as one of two lots; one of a minimum potency, designated Inv\_MMR\_Min; and the other at a mid-range or medium potency designated Inv\_MMR\_Med to two groups. The second dose for both of these Inv\_MMR groups will have a potency within the release range of the marketed vaccine. The Com\_MMR vaccine will consist of two lots designated Com\_MMR\_L1 and Com\_MMR\_L2 and will be analyzed as pooled lots within the study. The first MMR vaccine dose will be co-administered with Varivax, Havrix and (in the US sub-cohort only) Prevnar 13 which are routinely administered to children of this age in the US.
Interventions
BIOLOGICALPriorix
Subjects receive one dose of either minimum (Inv\_MMR\_Min) or medium (Inv\_MMR\_Med) potency lot at Day 0 and a dose of separate potency lot (Inv\_MMR\_Release) at Day 42, administered subcutaneously in the triceps region of the left arm.
BIOLOGICALM-M-R II
Subjects receive two doses of either Lot 1 or Lot 2, one at Day 0 and one at Day 42, administered subcutaneously in the triceps region of the left arm.
BIOLOGICALVarivax
Subjects receive one dose co-administered subcutaneously with the study vaccines (Priorix and M-M-R II), in the triceps region of right arm, at Day 0.
BIOLOGICALHavrix
Subjects receive one dose co-administered intramuscularly with the study vaccines (Priorix and M-M-R II), in the anterolateral region of the right thigh, at Day 0.
BIOLOGICALPrevnar 13
US Subjects receive one dose co-administered intramuscularly with the study vaccines (Priorix and M-M-R II), in the anterolateral region of the left thigh, at Day 0.
Sponsors
GlaxoSmithKline
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 with 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 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. * 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 (or ending at Visit 3 for the US post-dose 2 sub-cohort). Please Note: * Inactivated influenza (Flu) vaccine and Haemophilus influenzae type b conjugate vaccine (Hib) vaccines may be given at any time during the study, including the day of study vaccination (Flu and Hib vaccines must be administered at a different location than the study vaccine/s). * Any age appropriate vaccine may be given starting at Visit 2 (or starting at Visit 3 for the US post-dose 2 sub-cohort), 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, or at Visit 3 for the US post-dose 2 sub-cohort. * History of measles, mumps, rubella, varicella/zoster and/or hepatitis A diseases. * Known exposure to measles, mumps, rubella and/or varicella/zoster during the period starting 30 days prior to the 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. Acute disease is defined as the presence of a moderate or severe illness with or without fever. Fever is defined as temperature ≥38°C/100.4°F by any age appropriate route. 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: • A 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 (by Enzyme-linked Immunosorbent Assay [ELISA]) | At Day 42 | 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. |
| Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | At Day 42 | 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. |
| Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by Plaque Reduction Neutralization Test [PRNT]) | At Day 42 | 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. |
| Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | At Day 42 | 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. |
| Anti-measles Virus Antibody Concentrations (by ELISA) | At Day 42 | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. |
| Anti-mumps Virus Antibody Concentrations (by ELISA) | At Day 42 | Antibody concentrations were expressed as GMCs in EU/mL. |
| Anti-mumps Virus Antibody Concentrations (by PRNT) | At Day 42 | Antibody concentrations were expressed as Geometric Mean Titers (GMTs). |
| Anti-rubella Virus Antibody Concentrations (by ELISA) | At Day 42 | Antibody concentrations were expressed as GMCs in IU/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Any Solicited Local AEs Post Dose 2 | During the 4-day (Days 0-3) post-vaccination period | Assessed solicited local AEs were pain, redness and swelling. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination. |
| Number of Subjects With Any Solicited General AEs Post Dose 1 | During the 15-day (Days 0-14) post-vaccination period | 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. |
| Number of Subjects Reporting Any Fever Post Dose 1 | During the 43-day (Days 0-42) post-vaccination period | Any fever = Fever (axillary) ≥ 38°C. |
| Number of Subjects Reporting Any Rash Post Dose 1 | During the 43-day (Days 0-42) post-vaccination period | 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. |
| Number of Subjects Reporting Any Rash Post Dose 2 | During the 43-day (Days 0-42) post-vaccination period | 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. |
| Number of Subjects Reporting Any Fever Post Dose 2 | During the 43-day (Days 0-42) post-vaccination period | Any fever = Fever (axillary) ≥ 38°C. |
| Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 2 | During the 43-day (Days 0-42) post-vaccination period | 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. |
| Number of Subjects Reporting Any Unsolicited AES Post Dose 1 | During the 43-day (Days 0-42) post-vaccination period | 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. |
| Number of Subjects Reporting Any Unsolicited AES Post Dose 2 | During the 43-day (Days 0-42) post-vaccination period | 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. |
| Number of Subjects Reporting Any AEs of Specific Interest | From Day 0 through the end of the study (Day 222) | 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 the study (Day 222) | 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. |
| Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 1 | During the 43-day (Days 0-42) post-vaccination period | 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. |
| Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | At Day 84 | 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. |
| Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | At Day 84 | 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. |
| Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | At Day 84 | 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. |
| Anti-measles Virus Antibody Concentrations (by ELISA) | At Day 84 | Antibody concentrations were expressed as GMCs in mIU/mL. |
| Anti-mumps Virus Antibody Concentrations (by ELISA) | At Day 84 | Antibody concentrations were expressed as GMCs in EU/mL. |
| Anti-rubella Virus Antibody Concentrations (by ELISA) | At Day 84 | Antibody concentrations were expressed as GMCs in IU/mL. |
| Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1 | During the 4-day (Days 0-3) post-vaccination period | Assessed solicited local AEs were pain, redness and swelling. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination. |
Countries
Czechia, Finland, Malaysia, Puerto Rico, Spain, Thailand, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Inv_MMR_Min Group 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. | 1,493 |
| Inv_MMR_Med Group 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. | 1,497 |
| Com_MMR Group 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. | 1,526 |
| Total | 4,516 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 | 3 |
| Overall Study | As Per Sponsor Decision | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 36 | 38 | 53 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 27 | 30 | 25 |
Baseline characteristics
| Characteristic | Inv_MMR_Min Group | Inv_MMR_Med Group | Com_MMR Group | Total |
|---|---|---|---|---|
| Age, Continuous | 12.6 Months STANDARD_DEVIATION 0.9 | 12.6 Months STANDARD_DEVIATION 0.9 | 12.6 Months STANDARD_DEVIATION 0.9 | 12.6 Months STANDARD_DEVIATION 0.9 |
| Race/Ethnicity, Customized African Heritage / African American | 45 Participants | 53 Participants | 46 Participants | 144 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 3 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 362 Participants | 366 Participants | 367 Participants | 1095 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 55 Participants | 46 Participants | 49 Participants | 150 Participants |
| Race/Ethnicity, Customized White - Arabic / North African Heritage | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
| Race/Ethnicity, Customized White - Caucasian / European Heritage | 1017 Participants | 1022 Participants | 1052 Participants | 3091 Participants |
| Sex: Female, Male Female | 704 Participants | 718 Participants | 758 Participants | 2180 Participants |
| Sex: Female, Male Male | 789 Participants | 779 Participants | 768 Participants | 2336 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1,493 | 0 / 1,497 | 1 / 1,526 |
| other Total, other adverse events | 1,299 / 1,493 | 1,311 / 1,497 | 1,330 / 1,526 |
| serious Total, serious adverse events | 91 / 1,493 | 102 / 1,497 | 92 / 1,526 |
Outcome results
Primary
Anti-measles Virus Antibody Concentrations (by ELISA)
Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL.
Time frame: At Day 42
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Inv_MMR_Min Group | Anti-measles Virus Antibody Concentrations (by ELISA) | 2209.9 mIU/mL |
| Inv_MMR_Med Group | Anti-measles Virus Antibody Concentrations (by ELISA) | 2540.9 mIU/mL |
| Com_MMR Group | Anti-measles Virus Antibody Concentrations (by ELISA) | 2787.7 mIU/mL |
Comparison: Non-inferiority of Inv\_MMR\_Min vaccine compared to COM\_MMR vaccine in terms of GMCs for anti-measles antibodies at Day 42.97.5% CI: [0.72, 0.88]ANOVA
Comparison: Non-inferiority of Inv\_MMR\_Med vaccine compared to COM\_MMR vaccine in terms of GMCs for anti-measles antibodies at Day 42.97.5% CI: [0.83, 1.01]ANOVA
Primary
Anti-mumps Virus Antibody Concentrations (by ELISA)
Antibody concentrations were expressed as GMCs in EU/mL.
Time frame: At Day 42
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Inv_MMR_Min Group | Anti-mumps Virus Antibody Concentrations (by ELISA) | 58.7 EU/mL |
| Inv_MMR_Med Group | Anti-mumps Virus Antibody Concentrations (by ELISA) | 60.2 EU/mL |
| Com_MMR Group | Anti-mumps Virus Antibody Concentrations (by ELISA) | 71.6 EU/mL |
Comparison: Non-inferiority of Inv\_MMR\_Min vaccine compared to COM\_MMR vaccine in terms of GMCs for anti-mumps antibodies at Day 42.97.5% CI: [0.76, 0.89]ANOVA
Comparison: Non-inferiority of Inv\_MMR\_Med vaccine compared to COM\_MMR vaccine in terms of GMCs for anti-mumps antibodies at Day 42.97.5% CI: [0.78, 0.91]ANOVA
Primary
Anti-mumps Virus Antibody Concentrations (by PRNT)
Antibody concentrations were expressed as Geometric Mean Titers (GMTs).
Time frame: At Day 42
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Inv_MMR_Min Group | Anti-mumps Virus Antibody Concentrations (by PRNT) | 9.8 Titers |
| Inv_MMR_Med Group | Anti-mumps Virus Antibody Concentrations (by PRNT) | 10.7 Titers |
| Com_MMR Group | Anti-mumps Virus Antibody Concentrations (by PRNT) | 16.3 Titers |
Comparison: Non-inferiority of Inv\_MMR\_Min vaccine compared to COM\_MMR vaccine in terms of GMCs for anti-mumps antibodies at Day 42.97.5% CI: [0.53, 0.68]ANOVA
Comparison: Non-inferiority of Inv\_MMR\_Med vaccine compared to COM\_MMR vaccine in terms of GMCs for anti-mumps antibodies at Day 42.97.5% CI: [0.57, 0.74]ANOVA
Primary
Anti-rubella Virus Antibody Concentrations (by ELISA)
Antibody concentrations were expressed as GMCs in IU/mL.
Time frame: At Day 42
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Inv_MMR_Min Group | Anti-rubella Virus Antibody Concentrations (by ELISA) | 57.0 IU/mL |
| Inv_MMR_Med Group | Anti-rubella Virus Antibody Concentrations (by ELISA) | 56.9 IU/mL |
| Com_MMR Group | Anti-rubella Virus Antibody Concentrations (by ELISA) | 64.4 IU/mL |
Comparison: Non-inferiority of Inv\_MMR\_Min vaccine compared to COM\_MMR vaccine in terms of GMCs for anti-rubella antibodies at Day 42.97.5% CI: [0.83, 0.95]ANOVA
Comparison: Non-inferiority of Inv\_MMR\_Med vaccine compared to COM\_MMR vaccine in terms of GMCs for anti-rubella antibodies at Day 42.97.5% CI: [0.83, 0.95]ANOVA
Primary
Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by Enzyme-linked Immunosorbent Assay [ELISA])
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inv_MMR_Min Group | Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by Enzyme-linked Immunosorbent Assay [ELISA]) | Anti-measles ≥ 150 mIU/mL | 90.9 Percentage of subjects |
| Inv_MMR_Min Group | Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by Enzyme-linked Immunosorbent Assay [ELISA]) | Anti-measles ≥ 200 mIU/mL | 90.8 Percentage of subjects |
| Inv_MMR_Med Group | Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by Enzyme-linked Immunosorbent Assay [ELISA]) | Anti-measles ≥ 150 mIU/mL | 94.3 Percentage of subjects |
| Inv_MMR_Med Group | Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by Enzyme-linked Immunosorbent Assay [ELISA]) | Anti-measles ≥ 200 mIU/mL | 94.2 Percentage of subjects |
| Com_MMR Group | Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by Enzyme-linked Immunosorbent Assay [ELISA]) | Anti-measles ≥ 150 mIU/mL | 96.5 Percentage of subjects |
| Com_MMR Group | Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by Enzyme-linked Immunosorbent Assay [ELISA]) | Anti-measles ≥ 200 mIU/mL | 96.3 Percentage of subjects |
Comparison: Non-inferiority of Inv\_MMR\_Min vaccine compared to Com\_MMR vaccine in terms of seroresponse rate to measles virus at Day 42.97.5% CI: [-7.65, -3.43]
Comparison: Non-inferiority of Inv\_MMR\_Med vaccine compared to Com\_MMR vaccine in terms of seroresponse rate to measles virus at Day 42.97.5% CI: [-3.96, -0.27]
Primary
Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inv_MMR_Min Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | Anti-mumps ≥ 5 EU/mL | 99.1 Percentage of subjects |
| Inv_MMR_Min Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | Anti-mumps ≥ 10 EU/mL | 97.4 Percentage of subjects |
| Inv_MMR_Med Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | Anti-mumps ≥ 5 EU/mL | 99.0 Percentage of subjects |
| Inv_MMR_Med Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | Anti-mumps ≥ 10 EU/mL | 97.3 Percentage of subjects |
| Com_MMR Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | Anti-mumps ≥ 5 EU/mL | 99.2 Percentage of subjects |
| Com_MMR Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | Anti-mumps ≥ 10 EU/mL | 97.8 Percentage of subjects |
Comparison: Non-inferiority of Inv\_MMR\_Min vaccine compared to Com\_MMR vaccine in terms of seroresponse rate to mumps virus at Day 42.97.5% CI: [-1.91, 1.04]
Comparison: Non-inferiority of Inv\_MMR\_Med vaccine compared to Com\_MMR vaccine in terms of seroresponse rate to mumps virus at Day 42.97.5% CI: [-2.11, 0.91]
Primary
Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by Plaque Reduction Neutralization Test [PRNT])
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inv_MMR_Min Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by Plaque Reduction Neutralization Test [PRNT]) | ≥ 2.5 ED50 | 79.1 Percentage of subjects |
| Inv_MMR_Min Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by Plaque Reduction Neutralization Test [PRNT]) | ≥ 4 ED50 | 71.2 Percentage of subjects |
| Inv_MMR_Med Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by Plaque Reduction Neutralization Test [PRNT]) | ≥ 2.5 ED50 | 81.6 Percentage of subjects |
| Inv_MMR_Med Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by Plaque Reduction Neutralization Test [PRNT]) | ≥ 4 ED50 | 73.4 Percentage of subjects |
| Com_MMR Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by Plaque Reduction Neutralization Test [PRNT]) | ≥ 2.5 ED50 | 87.5 Percentage of subjects |
| Com_MMR Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by Plaque Reduction Neutralization Test [PRNT]) | ≥ 4 ED50 | 80.6 Percentage of subjects |
Comparison: Non-inferiority of Inv\_MMR\_Min vaccine compared to Com\_MMR vaccine in terms of seroresponse rate to mumps virus at Day 42.97.5% CI: [-13.2, -5.62]
Comparison: Non-inferiority of Inv\_MMR\_Med vaccine compared to Com\_MMR vaccine in terms of seroresponse rate to mumps virus at Day 42.97.5% CI: [-10.94, -3.49]
Primary
Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inv_MMR_Min Group | Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 4 IU/mL | 99.3 Percentage of subjects |
| Inv_MMR_Min Group | Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 10 IU/mL | 96.8 Percentage of subjects |
| Inv_MMR_Med Group | Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 4 IU/mL | 99.5 Percentage of subjects |
| Inv_MMR_Med Group | Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 10 IU/mL | 97.3 Percentage of subjects |
| Com_MMR Group | Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 4 IU/mL | 99.5 Percentage of subjects |
| Com_MMR Group | Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 10 IU/mL | 98.5 Percentage of subjects |
Comparison: Non-inferiority of Inv\_MMR\_Min vaccine compared to Com\_MMR vaccine in terms of seroresponse rate to rubella virus at Day 42.97.5% CI: [-3.11, -0.42]
Comparison: Non-inferiority of Inv\_MMR\_Med vaccine compared to Com\_MMR vaccine in terms of seroresponse rate to rubella virus at Day 42.97.5% CI: [-2.5, 0.05]
Secondary
Anti-measles Virus Antibody Concentrations (by ELISA)
Antibody concentrations were expressed as GMCs in mIU/mL.
Time frame: At Day 84
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Inv_MMR_Min Group | Anti-measles Virus Antibody Concentrations (by ELISA) | 4803.5 mIU/mL |
| Inv_MMR_Med Group | Anti-measles Virus Antibody Concentrations (by ELISA) | 4557.7 mIU/mL |
| Com_MMR Group | Anti-measles Virus Antibody Concentrations (by ELISA) | 4453.9 mIU/mL |
Secondary
Anti-mumps Virus Antibody Concentrations (by ELISA)
Antibody concentrations were expressed as GMCs in EU/mL.
Time frame: At Day 84
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Inv_MMR_Min Group | Anti-mumps Virus Antibody Concentrations (by ELISA) | 88.9 EU/mL |
| Inv_MMR_Med Group | Anti-mumps Virus Antibody Concentrations (by ELISA) | 94.1 EU/mL |
| Com_MMR Group | Anti-mumps Virus Antibody Concentrations (by ELISA) | 86.4 EU/mL |
Secondary
Anti-rubella Virus Antibody Concentrations (by ELISA)
Antibody concentrations were expressed as GMCs in IU/mL.
Time frame: At Day 84
Population: 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 | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Inv_MMR_Min Group | Anti-rubella Virus Antibody Concentrations (by ELISA) | 112.7 IU/mL |
| Inv_MMR_Med Group | Anti-rubella Virus Antibody Concentrations (by ELISA) | 110.7 IU/mL |
| Com_MMR Group | Anti-rubella Virus Antibody Concentrations (by ELISA) | 110.9 IU/mL |
Secondary
Number of Subjects Reporting Any 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 the study (Day 222)
Population: TVC included all vaccinated subjects with at least one vaccine administration of either Inv\_MMR lots or Com\_MMR lots documented.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Inv_MMR_Min Group | Number of Subjects Reporting Any AEs of Specific Interest | Any NOCD | 35 Participants |
| Inv_MMR_Min Group | Number of Subjects Reporting Any AEs of Specific Interest | Any AE prompting ER visit | 348 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any AEs of Specific Interest | Any NOCD | 39 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any AEs of Specific Interest | Any AE prompting ER visit | 361 Participants |
| Com_MMR Group | Number of Subjects Reporting Any AEs of Specific Interest | Any NOCD | 33 Participants |
| Com_MMR Group | Number of Subjects Reporting Any AEs of Specific Interest | Any AE prompting ER visit | 347 Participants |
Secondary
Number of Subjects Reporting Any Fever Post Dose 1
Any fever = Fever (axillary) ≥ 38°C.
Time frame: During the 43-day (Days 0-42) post-vaccination period
Population: TVC included all vaccinated subjects with at least one vaccine administration of either Inv\_MMR lots or Com\_MMR lots documented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inv_MMR_Min Group | Number of Subjects Reporting Any Fever Post Dose 1 | 582 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any Fever Post Dose 1 | 617 Participants |
| Com_MMR Group | Number of Subjects Reporting Any Fever Post Dose 1 | 618 Participants |
Secondary
Number of Subjects Reporting Any Fever Post Dose 2
Any fever = Fever (axillary) ≥ 38°C.
Time frame: During the 43-day (Days 0-42) post-vaccination period
Population: TVC included all vaccinated subjects with at least one vaccine administration of either Inv\_MMR lots or Com\_MMR lots documented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inv_MMR_Min Group | Number of Subjects Reporting Any Fever Post Dose 2 | 458 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any Fever Post Dose 2 | 471 Participants |
| Com_MMR Group | Number of Subjects Reporting Any Fever Post Dose 2 | 499 Participants |
Secondary
Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 1
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
Population: TVC included all vaccinated subjects with at least one vaccine administration of either Inv\_MMR lots or Com\_MMR lots documented.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Inv_MMR_Min Group | Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 1 | Any parotid gland swelling | 3 Participants |
| Inv_MMR_Min Group | Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 1 | Any febrile convulsion | 3 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 1 | Any parotid gland swelling | 2 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 1 | Any febrile convulsion | 4 Participants |
| Com_MMR Group | Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 1 | Any parotid gland swelling | 3 Participants |
| Com_MMR Group | Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 1 | Any febrile convulsion | 3 Participants |
Secondary
Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 2
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
Population: TVC included all vaccinated subjects with at least one vaccine administration of either Inv\_MMR lots or Com\_MMR lots documented.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Inv_MMR_Min Group | Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 2 | Any parotid gland swelling | 1 Participants |
| Inv_MMR_Min Group | Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 2 | Any febrile convulsion | 2 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 2 | Any parotid gland swelling | 2 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 2 | Any febrile convulsion | 6 Participants |
| Com_MMR Group | Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 2 | Any parotid gland swelling | 0 Participants |
| Com_MMR Group | Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 2 | Any febrile convulsion | 4 Participants |
Secondary
Number of Subjects Reporting Any Rash Post Dose 1
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
Population: TVC included all vaccinated subjects with at least one vaccine administration of either Inv\_MMR lots or Com\_MMR lots documented.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Inv_MMR_Min Group | Number of Subjects Reporting Any Rash Post Dose 1 | Any localized or generalized | 328 Participants |
| Inv_MMR_Min Group | Number of Subjects Reporting Any Rash Post Dose 1 | Any measles/rubella like | 53 Participants |
| Inv_MMR_Min Group | Number of Subjects Reporting Any Rash Post Dose 1 | Any with fever | 115 Participants |
| Inv_MMR_Min Group | Number of Subjects Reporting Any Rash Post Dose 1 | Any varicella like | 57 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any Rash Post Dose 1 | Any varicella like | 53 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any Rash Post Dose 1 | Any with fever | 133 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any Rash Post Dose 1 | Any measles/rubella like | 61 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any Rash Post Dose 1 | Any localized or generalized | 322 Participants |
| Com_MMR Group | Number of Subjects Reporting Any Rash Post Dose 1 | Any measles/rubella like | 68 Participants |
| Com_MMR Group | Number of Subjects Reporting Any Rash Post Dose 1 | Any with fever | 131 Participants |
| Com_MMR Group | Number of Subjects Reporting Any Rash Post Dose 1 | Any varicella like | 45 Participants |
| Com_MMR Group | Number of Subjects Reporting Any Rash Post Dose 1 | Any localized or generalized | 333 Participants |
Secondary
Number of Subjects Reporting Any Rash Post Dose 2
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
Population: TVC included all vaccinated subjects with at least one vaccine administration of either Inv\_MMR lots or Com\_MMR lots documented.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Inv_MMR_Min Group | Number of Subjects Reporting Any Rash Post Dose 2 | Any localized or generalized | 129 Participants |
| Inv_MMR_Min Group | Number of Subjects Reporting Any Rash Post Dose 2 | Any with fever | 52 Participants |
| Inv_MMR_Min Group | Number of Subjects Reporting Any Rash Post Dose 2 | Any varicella like | 0 Participants |
| Inv_MMR_Min Group | Number of Subjects Reporting Any Rash Post Dose 2 | Any measles/rubella like | 22 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any Rash Post Dose 2 | Any measles/rubella like | 14 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any Rash Post Dose 2 | Any localized or generalized | 150 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any Rash Post Dose 2 | Any varicella like | 0 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any Rash Post Dose 2 | Any with fever | 63 Participants |
| Com_MMR Group | Number of Subjects Reporting Any Rash Post Dose 2 | Any measles/rubella like | 14 Participants |
| Com_MMR Group | Number of Subjects Reporting Any Rash Post Dose 2 | Any with fever | 53 Participants |
| Com_MMR Group | Number of Subjects Reporting Any Rash Post Dose 2 | Any varicella like | 1 Participants |
| Com_MMR Group | Number of Subjects Reporting Any Rash Post Dose 2 | Any localized or generalized | 141 Participants |
Secondary
Number of Subjects Reporting Any Serious Adverse Events (SAEs)
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)
Population: TVC included all vaccinated subjects with at least one vaccine administration of either Inv\_MMR lots or Com\_MMR lots documented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inv_MMR_Min Group | Number of Subjects Reporting Any Serious Adverse Events (SAEs) | 91 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any Serious Adverse Events (SAEs) | 102 Participants |
| Com_MMR Group | Number of Subjects Reporting Any Serious Adverse Events (SAEs) | 92 Participants |
Secondary
Number of Subjects Reporting Any Unsolicited AES Post Dose 1
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
Population: TVC included all vaccinated subjects with at least one vaccine administration of either Inv\_MMR lots or Com\_MMR lots documented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inv_MMR_Min Group | Number of Subjects Reporting Any Unsolicited AES Post Dose 1 | 762 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any Unsolicited AES Post Dose 1 | 794 Participants |
| Com_MMR Group | Number of Subjects Reporting Any Unsolicited AES Post Dose 1 | 777 Participants |
Secondary
Number of Subjects Reporting Any Unsolicited AES Post Dose 2
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
Population: TVC included all vaccinated subjects with at least one vaccine administration of either Inv\_MMR lots or Com\_MMR lots documented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inv_MMR_Min Group | Number of Subjects Reporting Any Unsolicited AES Post Dose 2 | 667 Participants |
| Inv_MMR_Med Group | Number of Subjects Reporting Any Unsolicited AES Post Dose 2 | 703 Participants |
| Com_MMR Group | Number of Subjects Reporting Any Unsolicited AES Post Dose 2 | 690 Participants |
Secondary
Number of Subjects With Any Solicited General AEs Post Dose 1
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
Population: TVC included all vaccinated subjects with at least one vaccine administration of either Inv\_MMR lots or Com\_MMR lots documented.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Inv_MMR_Min Group | Number of Subjects With Any Solicited General AEs Post Dose 1 | Any irritability / fussiness | 749 Participants |
| Inv_MMR_Min Group | Number of Subjects With Any Solicited General AEs Post Dose 1 | Any drowsiness | 551 Participants |
| Inv_MMR_Min Group | Number of Subjects With Any Solicited General AEs Post Dose 1 | Any loss of appetite | 570 Participants |
| Inv_MMR_Med Group | Number of Subjects With Any Solicited General AEs Post Dose 1 | Any irritability / fussiness | 792 Participants |
| Inv_MMR_Med Group | Number of Subjects With Any Solicited General AEs Post Dose 1 | Any drowsiness | 565 Participants |
| Inv_MMR_Med Group | Number of Subjects With Any Solicited General AEs Post Dose 1 | Any loss of appetite | 589 Participants |
| Com_MMR Group | Number of Subjects With Any Solicited General AEs Post Dose 1 | Any drowsiness | 582 Participants |
| Com_MMR Group | Number of Subjects With Any Solicited General AEs Post Dose 1 | Any loss of appetite | 591 Participants |
| Com_MMR Group | Number of Subjects With Any Solicited General AEs Post Dose 1 | Any irritability / fussiness | 788 Participants |
Secondary
Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Inv_MMR_Min Group | Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1 | Any redness | 232 Participants |
| Inv_MMR_Min Group | Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1 | Any pain | 261 Participants |
| Inv_MMR_Min Group | Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1 | Any swelling | 89 Participants |
| Inv_MMR_Med Group | Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1 | Any redness | 256 Participants |
| Inv_MMR_Med Group | Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1 | Any pain | 262 Participants |
| Inv_MMR_Med Group | Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1 | Any swelling | 97 Participants |
| Com_MMR Group | Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1 | Any pain | 301 Participants |
| Com_MMR Group | Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1 | Any swelling | 122 Participants |
| Com_MMR Group | Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1 | Any redness | 286 Participants |
Secondary
Number of Subjects With Any Solicited Local AEs Post Dose 2
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
Population: TVC included all vaccinated subjects with at least one vaccine administration of either Inv\_MMR lots or Com\_MMR lots documented.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Inv_MMR_Min Group | Number of Subjects With Any Solicited Local AEs Post Dose 2 | Any redness | 159 Participants |
| Inv_MMR_Min Group | Number of Subjects With Any Solicited Local AEs Post Dose 2 | Any pain | 170 Participants |
| Inv_MMR_Min Group | Number of Subjects With Any Solicited Local AEs Post Dose 2 | Any swelling | 67 Participants |
| Inv_MMR_Med Group | Number of Subjects With Any Solicited Local AEs Post Dose 2 | Any redness | 196 Participants |
| Inv_MMR_Med Group | Number of Subjects With Any Solicited Local AEs Post Dose 2 | Any pain | 183 Participants |
| Inv_MMR_Med Group | Number of Subjects With Any Solicited Local AEs Post Dose 2 | Any swelling | 91 Participants |
| Com_MMR Group | Number of Subjects With Any Solicited Local AEs Post Dose 2 | Any pain | 196 Participants |
| Com_MMR Group | Number of Subjects With Any Solicited Local AEs Post Dose 2 | Any swelling | 96 Participants |
| Com_MMR Group | Number of Subjects With Any Solicited Local AEs Post Dose 2 | Any redness | 217 Participants |
Secondary
Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inv_MMR_Min Group | Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 150 mIU/mL | 99.6 Percentage of subjects |
| Inv_MMR_Min Group | Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 200 mIU/mL | 99.6 Percentage of subjects |
| Inv_MMR_Med Group | Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 150 mIU/mL | 98.8 Percentage of subjects |
| Inv_MMR_Med Group | Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 200 mIU/mL | 98.4 Percentage of subjects |
| Com_MMR Group | Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 150 mIU/mL | 98.8 Percentage of subjects |
| Com_MMR Group | Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 200 mIU/mL | 98.4 Percentage of subjects |
Secondary
Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inv_MMR_Min Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 5 EU/mL | 99.1 Percentage of subjects |
| Inv_MMR_Min Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 10 EU/mL | 99.1 Percentage of subjects |
| Inv_MMR_Med Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 5 EU/mL | 100 Percentage of subjects |
| Inv_MMR_Med Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 10 EU/mL | 100 Percentage of subjects |
| Com_MMR Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 5 EU/mL | 99.1 Percentage of subjects |
| Com_MMR Group | Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 10 EU/mL | 98.6 Percentage of subjects |
Secondary
Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inv_MMR_Min Group | Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 4 IU/mL | 100 Percentage of subjects |
| Inv_MMR_Min Group | Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 10 IU/mL | 99.6 Percentage of subjects |
| Inv_MMR_Med Group | Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 4 IU/mL | 100 Percentage of subjects |
| Inv_MMR_Med Group | Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 10 IU/mL | 99.6 Percentage of subjects |
| Com_MMR Group | Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 4 IU/mL | 100 Percentage of subjects |
| Com_MMR Group | Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA) | ≥ 10 IU/mL | 99.6 Percentage of subjects |