Rubella, Mumps, Measles
Conditions
Keywords
Measles, mumps and rubella diseases, Safety, Immunogenicity
Brief summary
The purpose of this study is to evaluate the immunogenicity and safety of GSK's trivalent MMR (Priorix®), comparing it to Mercks MMR vaccine (M-M-R®II), which is approved for use in the US.
Detailed description
This study will evaluate the immunogenicity of GSK's trivalent MMR vaccine (referred to as INV\_MMR vaccine) in contrast to the US standard of care (M-M-R®II, Merck and Company, referred to as COM\_MMR) when both are used as a second dose in subjects 7 years of age and older. In this study, the INV\_MMR vaccine may be administered as a second dose to persons with either a history or formal documentation of at least one dose immunization with any MMR vaccine. This study is intended to support licensure of GSK's MMR vaccine in the US.
Interventions
BIOLOGICALPriorix®
1 dose administered as a subcutaneous (SC) injection.
BIOLOGICALMerck's M-M-R®II, Measles, Mumps, and Rubella Virus Vaccine
1 dose administered subcutaneously.
Sponsors
Parexel
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
7 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that they and/or their parent(s) or Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol. * Male or female subjects 7 years of age or older and born after December 31, 1956\*. \*The only exception to this is health care workers born before 1957 without other evidence of immunity to mumps for which one dose of a live mumps virus vaccine is recommended; therefore this population is eligible for enrollment in this study. * For all children 7-17 years of age: * Written documentation of prior receipt of 1 dose of MMR vaccine administered on or after the first birthday. * For all adults 18 years of age and older: * Prior receipt (written or verbal history) of at least one dose of MMR vaccine. * Birth in the US. * Written informed consent obtained from the subject or from the parent(s)/LAR(s) of the subject (assent will be obtained from subjects who are still legally minors in line with local rules and regulations). * Subjects in stable health as determined by investigator's physical examination and assessment of subjects' medical history. * Female subjects of non-childbearing potential may be enrolled in the study. * Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, or ovariectomy or post-menopause. * Female subjects of childbearing potential may be enrolled in the study, if the subject * Has agreed to be abstinent or practiced adequate contraception during the entire period starting 30 days prior to vaccination(s) until 3 months after receipt of the study vaccination and * has a negative pregnancy test on the day of vaccination.
Exclusion criteria
* Child in care. * For all children 7-17 years of age: * Previous receipt of more than 1 dose of a measles-containing vaccine. * Use of any investigational or non-registered product other than the study vaccine(s), during the period starting 30 days preceding the day of study vaccination, (i.e. 30 days prior to Day 0) or planned use during the entire study period. * Receipt of any measles, mumps or rubella-containing vaccine during the period starting 42 days before the day of study vaccination (i.e. 42 days prior to Day 0). * Chronic administration (defined as 14 or more consecutive days) of immunosuppressants or other immune-modifying drugs during the period starting 180 days before study vaccination or any planned administration of immune-modifying drugs during the entire study. Inhaled and topical steroids are allowed. * Administration of immunoglobulins and/or any blood products during the period starting 180 days prior to study vaccination through the immunogenicity evaluation at Visit 2 or Visit 3 (for one-dose or two-dose cohort, respectively). * Planned administration/ administration of any live viral vaccine not foreseen by the study protocol during the period starting 30 days prior to study vaccination and ending at Visit 2. Live intranasal influenza vaccine or any inactivated vaccine required in the age group may be given at any time, including the day of study vaccination. * Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product. * History of measles, mumps, or rubella disease. * Known exposure to measles, mumps, or rubella, during the period starting 30 days before study start (i.e. 30 days prior to Day 0). * %
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-measles Virus Antibody Concentrations. | At Day 42 | Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in milli International Units per milliliter (mIU/mL). Seropositivity was defined as subjects with anti-measles virus antibody concentration equal or greater than 150 mIU/mL. |
| Anti-mumps Virus Antibody Concentrations | At Day 42 | Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in EU/mL. Seropositivity was defined as subjects with anti-mumps virus antibody concentration equal or greater than 5 EU/mL |
| Anti-rubella Virus Antibody Concentrations. | At Day 42 | Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in IU/mL. Seropositivity was defined as subjects with anti-rubella virus antibody concentration equal or greater than 4 IU/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Anti-rubella Virus Antibody Concentration Equal or Above the Threshold of 10 IU/mL (Seroresponse Rate). | At Day 42 | Seroresponse was defined as: Anti-rubella virus antibody concentration equal to or above the threshold of 10 IU/mL after administration of INV\_MMR vaccine vs. COM\_MMR at Day 42. |
| Number of Subjects Who Achieved a 4-fold or Greater Rise in Anti-measles, Anti-mumps and Anti-rubella Virus Antibody Concentrations. | At Day 42 | For subjects with seronegative status at pre-vaccination, a 4-fold rise in antibody concentration is defined as 4 times the cut-off level of the assay. Cut-off levels for anti-measles, anti-mumps and anti-rubella virus antibody concentrations are 150 mIU/mL, 5 EU/mL and 4 IU/mL. |
| Number of Subjects With Solicited Local Symptoms | During the 4-day (Days 0-3) post-vaccination period | Assessed solicited local symptoms were pain, redness and swelling. Any = Occurrence of any local symptom regardless of their intensity grade. Grade 3 Pain = Significant pain at rest. Prevented normal every day activities. Grade 3 redness = redness with surface diameter \>50mm. Grade 3 swelling = swelling with surface diameter \>50mm. |
| Number of Subjects Reporting Fever | During the 43 days (Days 0-42) post-vaccination period. | Fever was assessed:Any fever (≥38°C) = occurrence of any fever regardless of its intensity grade or relationship to vaccination. Grade3 fever = fever \>39.5°C. . Related = symptom assessed by the investigator as causally related to study vaccination.The preferred route for recording temperature in this study was oral. |
| Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure. | During the 43 days (Days 0-42) post-vaccination period. | Assessed MMR specific symptoms were parotid/salivary gland swelling and any sign of meningism/seizure. Parotid/salivary gland swelling: Any = occurrence of any general symptoms regardless of their intensity grade or relationship to vaccination; Grade 3 Parotid/salivary gland swelling = Swelling accompanied with general symptoms. Meningism/seizure: Any= occurrence of any general symptoms regardless of their intensity grade or relationship to vaccination; Grade-3 meningism/seizure= Prevented normal, everyday activities (In adults/adolescents, such an AE could, for example, prevented attendance at work/school and could necessitated the administration of corrective therapy). Related symptom = symptom assessed by the investigator as causally related to study vaccination. |
| Number of Subjects Reporting Unsolicited AEs | During the 43 days (Days 0-42) post-vaccination period. | Any untoward medical occurrence in a patient or clinical investigation child, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product |
| Number of Subjects Reporting Solicited Joint Pain (Arthralgia/Arthritis) | During the 43 days (Days 0-42) post-vaccination period. | Assessed any, Grade-3, Related. Any= occurrence of any general symptom regardless of its intensity grade or relationship to vaccination; Grade3 joint pain (arthralgia/arthritis)= Pain which prevented normal, everyday activities (In adults/adolescents, such an AE could, for example, prevented attendance at work/school and could necessitated the administration of corrective therapy). Related = symptom assessed by the investigator as causally related to study vaccination. |
| Number of Subjects Reporting NOCDs | Day 0 through the end of the study (Day 180) | Occurrence of new onset chronic diseases (NOCDs) |
| Number of Subjects Reporting Adverse Events Prompting ER Visits | Day 0 through the end of the study (Day 180) | Occurrence of AEs prompting emergency room (ER) visits. |
| Number of Subjects Reporting Serious Adverse Events (SAEs) | Day 0 through the end of the study (Day 180) | A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity. |
| Number of Subjects Reporting Solicited Rash Symptom | During the 43 days (Days 0-42) post-vaccination period. | Assessed any rash, Grade 3, Related, Localized rash, Generalized rash,measles/rubella-rash. Any= occurrence of any general symptom regardless of its intensity grade or relationship to vaccination. Grade3 rash/exanthema= Rash which prevented normal, everyday activities (In adults/adolescents, such an AE could, for example, prevented attendance at work/school and could necessitated the administration of corrective therapy). Grade 3 measles/rubella/varicella-like rash = Rash with more than150 lesions. Related = symptom assessed by the investigator as causally related to study vaccination. |
| Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Threshold of 200 mIU/mL (Seroresponse Rate) | At Day 42 | Seroresponse was defined as: Anti-measles virus antibody concentration equal to or above the threshold of 200 mIU/mL after administration of INV\_MMR vaccine vs. COM\_MMR at Day 42. |
| Number of Subjects With Anti-mumps Virus Antibody Concentration Equal or Above the Threshold of 10 EU/mL (Seroresponse Rate). | At Day 42 | Seroresponse was defined as: Anti-mumps virus antibody concentration equal to or above the threshold of 10 EU/mL after administration of INV\_MMR vaccine vs. COM\_MMR at Day 42. |
Countries
Estonia, Slovakia, United States
Participant flow
Recruitment details
A total of 996 subjects were enrolled and 994 were vaccinated. Of the 994 vaccinated subjects, 83 subjects from 2 US sites were excluded due to significant GCP concerns, resulting in 911 subjects in the Total vaccinated cohort considered for the analysis.
Participants by arm
| Arm | Count |
|---|---|
| INV_MMR Group Subjects received one dose of INV\_MMR (Priorix®) vaccine at Visit 1 (Day 0). | 454 |
| COM_MMR Group Subjects received one dose of COM\_MMR (M-M-R®II) vaccine from Lot 1 or Lot 2 at Visit 1 (Day 0). | 457 |
| Total | 911 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Consent Withdrawal | 1 | 1 |
| Overall Study | Lost to Follow-up | 26 | 22 |
| Overall Study | Other (patient incarcerated) | 0 | 1 |
| Overall Study | Other (vaccinated later as new subject) | 1 | 0 |
Baseline characteristics
| Characteristic | COM_MMR Group | Total | INV_MMR Group |
|---|---|---|---|
| Age, Continuous | 25.6 Months STANDARD_DEVIATION 13.8 | 25.7 Months STANDARD_DEVIATION 13.8 | 25.9 Months STANDARD_DEVIATION 13.9 |
| Race/Ethnicity, Customized African Heritage/African American | 103 Participants | 211 Participants | 108 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan native | 4 Participants | 6 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian heritage | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - East Asian heritage | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - Japanese heritage | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - South East Asian heritage | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 11 Participants | 7 Participants |
| Race/Ethnicity, Customized White - Arabic/North African heritage | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White - Caucasian/European heritage | 344 Participants | 678 Participants | 334 Participants |
| Sex: Female, Male Female | 252 Participants | 502 Participants | 250 Participants |
| Sex: Female, Male Male | 205 Participants | 409 Participants | 204 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 93 / 454 | 102 / 457 |
| serious Total, serious adverse events | 3 / 454 | 7 / 457 |
Outcome results
Primary
Anti-measles Virus Antibody Concentrations.
Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in milli International Units per milliliter (mIU/mL). Seropositivity was defined as subjects with anti-measles virus antibody concentration equal or greater than 150 mIU/mL.
Time frame: At Day 42
Population: ATP cohort for immunogenicity: included all eligible subjects with post-dose serology results available for at least one antigen of measles, mumps, or rubella, who complied with the protocol, who did not meet any elimination criteria and had no intercurrent medical conditions leading to elimination up to the Visit 2 (Day 42) blood sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| INV_MMR Group | Anti-measles Virus Antibody Concentrations. | 1795.6 mIU/mL |
| COM_MMR Group | Anti-measles Virus Antibody Concentrations. | 1783.3 mIU/mL |
Comparison: Non-inferiority of INV\_MMR vaccine to COM\_MMR vaccine in terms of Geometric Mean Concentration (GMCs) for anti measles, anti mumps and anti rubella antibodies at Day 42.The 95% CI for adjusted geometric mean concentrations (GMCs) and the adjusted GMC ratio were obtained using an ANCOVA model on the logarithm-transformed concentrations including the vaccine group (for adjusted GMC ratio) as fixed effect, gender, age and country groups as continuous effects and the pre-vaccination log-transformed95% CI: [0.91, 1.11]
Primary
Anti-mumps Virus Antibody Concentrations
Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in EU/mL. Seropositivity was defined as subjects with anti-mumps virus antibody concentration equal or greater than 5 EU/mL
Time frame: At Day 42
Population: ATP cohort for immunogenicity: included all eligible subjects with post-dose serology results available for at least one antigen of measles, mumps, or rubella, who complied with the protocol, who did not meet any elimination criteria and had no intercurrent medical conditions leading to elimination up to the Visit 2 (Day 42) blood sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| INV_MMR Group | Anti-mumps Virus Antibody Concentrations | 110.6 EU/mL |
| COM_MMR Group | Anti-mumps Virus Antibody Concentrations | 110.2 EU/mL |
Comparison: Non-inferiority of INV\_MMR vaccine to COM\_MMR vaccine in terms of Geometric Mean Concentration (GMCs) for anti measles, anti mumps and anti rubella antibodies at Day 42.The 95% CI for adjusted geometric mean concentrations (GMCs) and the adjusted GMC ratio were obtained using an ANCOVA model on the logarithm-transformed concentrations including the vaccine group (for adjusted GMC ratio) as fixed effect, gender, age and country groups as continuous effects and the pre-vaccination log-transformed.95% CI: [0.96, 1.16]
Primary
Anti-rubella Virus Antibody Concentrations.
Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in IU/mL. Seropositivity was defined as subjects with anti-rubella virus antibody concentration equal or greater than 4 IU/mL
Time frame: At Day 42
Population: ATP cohort for immunogenicity: included all eligible subjects with post-dose serology results available for at least one antigen of measles, mumps, or rubella, who complied with the protocol, who did not meet any elimination criteria and had no intercurrent medical conditions leading to elimination up to the Visit 2 (Day 42) blood sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| INV_MMR Group | Anti-rubella Virus Antibody Concentrations. | 75.3 IU/mL |
| COM_MMR Group | Anti-rubella Virus Antibody Concentrations. | 75.6 IU/mL |
Comparison: Non-inferiority of INV\_MMR vaccine to COM\_MMR vaccine in terms of Geometric Mean Concentration (GMCs) for anti measles, anti mumps and anti rubella antibodies at Day 42.The 95% CI for adjusted geometric mean concentrations (GMCs) and the adjusted GMC ratio were obtained using an ANCOVA model on the logarithm-transformed concentrations including the vaccine group (for adjusted GMC ratio) as fixed effect, gender, age and country groups as continuous effects and the pre-vaccination log-transformed95% CI: [0.93, 1.11]
Secondary
Number of Subjects Reporting Adverse Events Prompting ER Visits
Occurrence of AEs prompting emergency room (ER) visits.
Time frame: Day 0 through the end of the study (Day 180)
Population: Total Vaccinated cohort included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| INV_MMR Group | Number of Subjects Reporting Adverse Events Prompting ER Visits | 14 Subjects |
| COM_MMR Group | Number of Subjects Reporting Adverse Events Prompting ER Visits | 9 Subjects |
Secondary
Number of Subjects Reporting Fever
Fever was assessed:Any fever (≥38°C) = occurrence of any fever regardless of its intensity grade or relationship to vaccination. Grade3 fever = fever \>39.5°C. . Related = symptom assessed by the investigator as causally related to study vaccination.The preferred route for recording temperature in this study was oral.
Time frame: During the 43 days (Days 0-42) post-vaccination period.
Population: Total Vaccinated cohort included all vaccinated subjects with a documented vaccine administration.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| INV_MMR Group | Number of Subjects Reporting Fever | Any | 13 Subjects |
| INV_MMR Group | Number of Subjects Reporting Fever | Grade 3 | 1 Subjects |
| INV_MMR Group | Number of Subjects Reporting Fever | Related | 2 Subjects |
| COM_MMR Group | Number of Subjects Reporting Fever | Any | 23 Subjects |
| COM_MMR Group | Number of Subjects Reporting Fever | Grade 3 | 6 Subjects |
| COM_MMR Group | Number of Subjects Reporting Fever | Related | 6 Subjects |
Secondary
Number of Subjects Reporting NOCDs
Occurrence of new onset chronic diseases (NOCDs)
Time frame: Day 0 through the end of the study (Day 180)
Population: Total Vaccinated cohort included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| INV_MMR Group | Number of Subjects Reporting NOCDs | 2 Subjects |
| COM_MMR Group | Number of Subjects Reporting NOCDs | 1 Subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs)
A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity.
Time frame: Day 0 through the end of the study (Day 180)
Population: Total Vaccinated cohort included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| INV_MMR Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 3 Subjects |
| COM_MMR Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 7 Subjects |
Secondary
Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure.
Assessed MMR specific symptoms were parotid/salivary gland swelling and any sign of meningism/seizure. Parotid/salivary gland swelling: Any = occurrence of any general symptoms regardless of their intensity grade or relationship to vaccination; Grade 3 Parotid/salivary gland swelling = Swelling accompanied with general symptoms. Meningism/seizure: Any= occurrence of any general symptoms regardless of their intensity grade or relationship to vaccination; Grade-3 meningism/seizure= Prevented normal, everyday activities (In adults/adolescents, such an AE could, for example, prevented attendance at work/school and could necessitated the administration of corrective therapy). Related symptom = symptom assessed by the investigator as causally related to study vaccination.
Time frame: During the 43 days (Days 0-42) post-vaccination period.
Population: Total Vaccinated cohort included all vaccinated subjects with a documented vaccine administration.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| INV_MMR Group | Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure. | Any parotid/salivary gland swelling | 1 Subjects |
| INV_MMR Group | Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure. | Grade 3 parotid/salivary gland swelling | 1 Subjects |
| INV_MMR Group | Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure. | Related parotid/salivary gland swelling | 0 Subjects |
| INV_MMR Group | Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure. | Any meningism/seizure | 1 Subjects |
| INV_MMR Group | Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure. | Grade 3 meningism/seizure | 1 Subjects |
| INV_MMR Group | Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure. | Related meningism/seizure | 0 Subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure. | Grade 3 meningism/seizure | 0 Subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure. | Any parotid/salivary gland swelling | 1 Subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure. | Any meningism/seizure | 1 Subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure. | Grade 3 parotid/salivary gland swelling | 0 Subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure. | Related meningism/seizure | 0 Subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure. | Related parotid/salivary gland swelling | 0 Subjects |
Secondary
Number of Subjects Reporting Solicited Joint Pain (Arthralgia/Arthritis)
Assessed any, Grade-3, Related. Any= occurrence of any general symptom regardless of its intensity grade or relationship to vaccination; Grade3 joint pain (arthralgia/arthritis)= Pain which prevented normal, everyday activities (In adults/adolescents, such an AE could, for example, prevented attendance at work/school and could necessitated the administration of corrective therapy). Related = symptom assessed by the investigator as causally related to study vaccination.
Time frame: During the 43 days (Days 0-42) post-vaccination period.
Population: Total Vaccinated cohort included all vaccinated subjects with a documented vaccine administration.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| INV_MMR Group | Number of Subjects Reporting Solicited Joint Pain (Arthralgia/Arthritis) | Any | 8 subjects |
| INV_MMR Group | Number of Subjects Reporting Solicited Joint Pain (Arthralgia/Arthritis) | Grade 3 | 0 subjects |
| INV_MMR Group | Number of Subjects Reporting Solicited Joint Pain (Arthralgia/Arthritis) | Related | 3 subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited Joint Pain (Arthralgia/Arthritis) | Any | 4 subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited Joint Pain (Arthralgia/Arthritis) | Grade 3 | 0 subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited Joint Pain (Arthralgia/Arthritis) | Related | 1 subjects |
Secondary
Number of Subjects Reporting Solicited Rash Symptom
Assessed any rash, Grade 3, Related, Localized rash, Generalized rash,measles/rubella-rash. Any= occurrence of any general symptom regardless of its intensity grade or relationship to vaccination. Grade3 rash/exanthema= Rash which prevented normal, everyday activities (In adults/adolescents, such an AE could, for example, prevented attendance at work/school and could necessitated the administration of corrective therapy). Grade 3 measles/rubella/varicella-like rash = Rash with more than150 lesions. Related = symptom assessed by the investigator as causally related to study vaccination.
Time frame: During the 43 days (Days 0-42) post-vaccination period.
Population: Total Vaccinated cohort included all vaccinated subjects with a documented vaccine administration.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| INV_MMR Group | Number of Subjects Reporting Solicited Rash Symptom | Related | 6 Subjects |
| INV_MMR Group | Number of Subjects Reporting Solicited Rash Symptom | Generalized rash | 1 Subjects |
| INV_MMR Group | Number of Subjects Reporting Solicited Rash Symptom | Grade 3 | 0 Subjects |
| INV_MMR Group | Number of Subjects Reporting Solicited Rash Symptom | Rash type - measles/rubella-rash | 0 Subjects |
| INV_MMR Group | Number of Subjects Reporting Solicited Rash Symptom | Localized rash | 8 Subjects |
| INV_MMR Group | Number of Subjects Reporting Solicited Rash Symptom | Rash type - others | 9 Subjects |
| INV_MMR Group | Number of Subjects Reporting Solicited Rash Symptom | Any | 9 Subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited Rash Symptom | Rash type - others | 3 Subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited Rash Symptom | Any | 5 Subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited Rash Symptom | Grade 3 | 0 Subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited Rash Symptom | Related | 2 Subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited Rash Symptom | Localized rash | 3 Subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited Rash Symptom | Generalized rash | 2 Subjects |
| COM_MMR Group | Number of Subjects Reporting Solicited Rash Symptom | Rash type - measles/rubella-rash | 2 Subjects |
Secondary
Number of Subjects Reporting Unsolicited AEs
Any untoward medical occurrence in a patient or clinical investigation child, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
Time frame: During the 43 days (Days 0-42) post-vaccination period.
Population: Total Vaccinated cohort included all vaccinated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| INV_MMR Group | Number of Subjects Reporting Unsolicited AEs | 95 Subjects |
| COM_MMR Group | Number of Subjects Reporting Unsolicited AEs | 82 Subjects |
Secondary
Number of Subjects Who Achieved a 4-fold or Greater Rise in Anti-measles, Anti-mumps and Anti-rubella Virus Antibody Concentrations.
For subjects with seronegative status at pre-vaccination, a 4-fold rise in antibody concentration is defined as 4 times the cut-off level of the assay. Cut-off levels for anti-measles, anti-mumps and anti-rubella virus antibody concentrations are 150 mIU/mL, 5 EU/mL and 4 IU/mL.
Time frame: At Day 42
Population: ATP cohort for immunogenicity: included all eligible subjects with post-dose serology results available for at least one antigen of measles, mumps, or rubella, who complied with the protocol, who did not meet any elimination criteria and had no intercurrent medical conditions leading to elimination up to the Visit 2 (Day 42) blood sample.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| INV_MMR Group | Number of Subjects Who Achieved a 4-fold or Greater Rise in Anti-measles, Anti-mumps and Anti-rubella Virus Antibody Concentrations. | Anti-measles | 42 Subjects |
| INV_MMR Group | Number of Subjects Who Achieved a 4-fold or Greater Rise in Anti-measles, Anti-mumps and Anti-rubella Virus Antibody Concentrations. | Anti-mumps | 152 Subjects |
| INV_MMR Group | Number of Subjects Who Achieved a 4-fold or Greater Rise in Anti-measles, Anti-mumps and Anti-rubella Virus Antibody Concentrations. | Anti-rubella | 179 Subjects |
| COM_MMR Group | Number of Subjects Who Achieved a 4-fold or Greater Rise in Anti-measles, Anti-mumps and Anti-rubella Virus Antibody Concentrations. | Anti-measles | 48 Subjects |
| COM_MMR Group | Number of Subjects Who Achieved a 4-fold or Greater Rise in Anti-measles, Anti-mumps and Anti-rubella Virus Antibody Concentrations. | Anti-mumps | 128 Subjects |
| COM_MMR Group | Number of Subjects Who Achieved a 4-fold or Greater Rise in Anti-measles, Anti-mumps and Anti-rubella Virus Antibody Concentrations. | Anti-rubella | 161 Subjects |
Secondary
Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Threshold of 200 mIU/mL (Seroresponse Rate)
Seroresponse was defined as: Anti-measles virus antibody concentration equal to or above the threshold of 200 mIU/mL after administration of INV\_MMR vaccine vs. COM\_MMR at Day 42.
Time frame: At Day 42
Population: ATP cohort for immunogenicity: included all eligible subjects with post-dose serology results available for at least one antigen of measles, mumps, or rubella, who complied with the protocol, who did not meet any elimination criteria and had no intercurrent medical conditions leading to elimination up to the Visit 2 (Day 42) blood sample.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| INV_MMR Group | Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Threshold of 200 mIU/mL (Seroresponse Rate) | 428 Subjects |
| COM_MMR Group | Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Threshold of 200 mIU/mL (Seroresponse Rate) | 432 Subjects |
Secondary
Number of Subjects With Anti-mumps Virus Antibody Concentration Equal or Above the Threshold of 10 EU/mL (Seroresponse Rate).
Seroresponse was defined as: Anti-mumps virus antibody concentration equal to or above the threshold of 10 EU/mL after administration of INV\_MMR vaccine vs. COM\_MMR at Day 42.
Time frame: At Day 42
Population: ATP cohort for immunogenicity: included all eligible subjects with post-dose serology results available for at least one antigen of measles, mumps, or rubella, who complied with the protocol, who did not meet any elimination criteria and had no intercurrent medical conditions leading to elimination up to the Visit 2 (Day 42) blood sample.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| INV_MMR Group | Number of Subjects With Anti-mumps Virus Antibody Concentration Equal or Above the Threshold of 10 EU/mL (Seroresponse Rate). | 426 Subjects |
| COM_MMR Group | Number of Subjects With Anti-mumps Virus Antibody Concentration Equal or Above the Threshold of 10 EU/mL (Seroresponse Rate). | 434 Subjects |
Secondary
Number of Subjects With Anti-rubella Virus Antibody Concentration Equal or Above the Threshold of 10 IU/mL (Seroresponse Rate).
Seroresponse was defined as: Anti-rubella virus antibody concentration equal to or above the threshold of 10 IU/mL after administration of INV\_MMR vaccine vs. COM\_MMR at Day 42.
Time frame: At Day 42
Population: ATP cohort for immunogenicity: included all eligible subjects with post-dose serology results available for at least one antigen of measles, mumps, or rubella, who complied with the protocol, who did not meet any elimination criteria and had no intercurrent medical conditions leading to elimination up to the Visit 2 (Day 42) blood sample.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| INV_MMR Group | Number of Subjects With Anti-rubella Virus Antibody Concentration Equal or Above the Threshold of 10 IU/mL (Seroresponse Rate). | 431 Subjects |
| COM_MMR Group | Number of Subjects With Anti-rubella Virus Antibody Concentration Equal or Above the Threshold of 10 IU/mL (Seroresponse Rate). | 435 Subjects |
Secondary
Number of Subjects With Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = Occurrence of any local symptom regardless of their intensity grade. Grade 3 Pain = Significant pain at rest. Prevented normal every day activities. Grade 3 redness = redness with surface diameter \>50mm. Grade 3 swelling = swelling with surface diameter \>50mm.
Time frame: During the 4-day (Days 0-3) post-vaccination period
Population: Total Vaccinated cohort included all vaccinated subjects with a documented vaccine administration.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| INV_MMR Group | Number of Subjects With Solicited Local Symptoms | Any injection site pain | 51 Subjects |
| INV_MMR Group | Number of Subjects With Solicited Local Symptoms | Grade 3 injection site redness | 0 Subjects |
| INV_MMR Group | Number of Subjects With Solicited Local Symptoms | Any injection site swelling | 23 Subjects |
| INV_MMR Group | Number of Subjects With Solicited Local Symptoms | Grade 3 injection site swelling | 0 Subjects |
| INV_MMR Group | Number of Subjects With Solicited Local Symptoms | Grade 3 injection site pain | 1 Subjects |
| INV_MMR Group | Number of Subjects With Solicited Local Symptoms | Any injection site redness | 53 Subjects |
| COM_MMR Group | Number of Subjects With Solicited Local Symptoms | Grade 3 injection site pain | 0 Subjects |
| COM_MMR Group | Number of Subjects With Solicited Local Symptoms | Any injection site redness | 52 Subjects |
| COM_MMR Group | Number of Subjects With Solicited Local Symptoms | Any injection site pain | 51 Subjects |
| COM_MMR Group | Number of Subjects With Solicited Local Symptoms | Grade 3 injection site redness | 0 Subjects |
| COM_MMR Group | Number of Subjects With Solicited Local Symptoms | Grade 3 injection site swelling | 0 Subjects |
| COM_MMR Group | Number of Subjects With Solicited Local Symptoms | Any injection site swelling | 29 Subjects |