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    Clinical Trial Results:
    An open-label, randomised, comparative, multi-centre study of the immunogenicity and safety of a 2-dose regimen of ProQuad® manufactured with rHA administered to healthy children from 9 months of age

    Due to a system error, the data reported in v1 is not correct and has been removed from public view.
    Summary
    EudraCT number
    2007-002468-88
    Trial protocol
    FR   DE   FI  
    Global end of trial date
    29 Dec 2008

    Results information
    Results version number
    v2(current)
    This version publication date
    11 May 2016
    First version publication date
    11 Jun 2015
    Other versions
    v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    Correction of data in the "Adverse Events" section.

    Trial information

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    Trial identification
    Sponsor protocol code
    MRV02C
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00566527
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Sanofi Pasteur MSD S.N.C.
    Sponsor organisation address
    162 avenue Jean Jaurès - CS 50712, Lyon Cedex 07, France, 69367
    Public contact
    Clinical Trials Disclosure, Sanofi Pasteur MSD S.N.C., ClinicalTrialsDisclosure@spmsd.com
    Scientific contact
    Clinical Trials Disclosure, Sanofi Pasteur MSD S.N.C., ClinicalTrialsDisclosure@spmsd.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Dec 2008
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Dec 2008
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    # 1st primary objective: to demonstrate that a 2-dose regimen of ProQuad administered at a 3-month interval to healthy children of 11 months of age at the time of Dose 1 was as immunogenic as in healthy children of 12 months of age at the time of Dose 1, in terms of antibody response rates to measles, mumps, rubella and varicella at Day 42 following Dose 2. # 2nd primary objective (only if the 1st primary objective was reached): similar to the 1st one at 9 months of age. # 3rd primary objective: to demonstrate that a 2-dose regimen of ProQuad administered at a 3-month interval to healthy children of 11 months of age and 9 months of age at the time of Dose 1 is well tolerated compared to healthy children of 12 months of age at the time of Dose 1. Note: "ProQuad® manufactured with rHA" (recombinant Human Albumin) was referred to "ProQuad" to facilitate the reading.
    Protection of trial subjects
    Subjects with prior known sensitivity or allergy to any component of the vaccine (including neomycin, sorbitol or gelatin) or true allergy to egg proteins (anaphylactic or anaphylactoid reaction after ingesting eggs) were not vaccinated. Vaccines were administered by qualified study personnel. After each vaccination, subjects were kept under observation for at least 20 minutes to ensure their safety.
    Background therapy
    -
    Evidence for comparator
    The objective of this study was to provide sufficient data for a change in the indication of the Dose 1 of ProQuad from 12 months of age to the lowest possible age (11 months or 9 months). Therefore, subjects receiving ProQuad Dose 1 at 12 months of age constituted the "active comparator" arm of this study. In the experimental arms, subjects received ProQuad Dose 1 at 11 or 9 months of age.
    Actual start date of recruitment
    29 Nov 2007
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Finland: 1290
    Country: Number of subjects enrolled
    France: 140
    Country: Number of subjects enrolled
    Germany: 190
    Worldwide total number of subjects
    1620
    EEA total number of subjects
    1620
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    1620
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Study subjects were enrolled between 29 November 2007 and 14 April 2008 in 48 active centres in 3 European countries (Finland, France and Germany).

    Pre-assignment
    Screening details
    1626 subjects were screened out. 1620 subjects were randomised and constituted the population of the study. 1483 subjects received at least 1 dose of ProQuad. 1465 subjects received the 2 doses of ProQuad. 1459 subjects completed the study.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded
    Blinding implementation details
    This was an open-label study. Therefore, neither blinding procedure nor emergency identification of investigational vaccine was necessary.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    ProQuad - 9 months
    Arm description
    Subjects received 2 doses of ProQuad (measles, mumps, rubella and varicella (live attenuated)) vaccine: the 1st dose was administered at 9 months of age, and the 2nd dose 90 days later.
    Arm type
    Experimental

    Investigational medicinal product name
    ProQuad® manufactured with rHA
    Investigational medicinal product code
    MMRV
    Other name
    ProQuad
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    0.5 mL, subcutaneous route (deltoid region, upper arm), 2 doses with a 3-month interval. Both doses had to be administered in the opposite arm to the blood sampling.

    Arm title
    ProQuad - 11 months
    Arm description
    Subjects received 2 doses of ProQuad (measles, mumps, rubella and varicella (live attenuated)) vaccine: the 1st dose was administered at 11 months of age, and the 2nd dose 90 days later.
    Arm type
    Experimental

    Investigational medicinal product name
    ProQuad® manufactured with rHA
    Investigational medicinal product code
    MMRV
    Other name
    ProQuad
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    0.5 mL, subcutaneous route (deltoid region, upper arm), 2 doses with a 3-month interval. Both doses had to be administered in the opposite arm to the blood sampling.

    Arm title
    ProQuad - 12 months
    Arm description
    Subjects received 2 doses of ProQuad (measles, mumps, rubella and varicella (live attenuated)) vaccine: the 1st dose was administered at 12 months of age, and the 2nd dose 90 days later.
    Arm type
    Active comparator

    Investigational medicinal product name
    ProQuad® manufactured with rHA
    Investigational medicinal product code
    MMRV
    Other name
    ProQuad
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    0.5 mL, subcutaneous route (deltoid region, upper arm), 2 doses with a 3-month interval. Both doses had to be administered in the opposite arm to the blood sampling.

    Number of subjects in period 1
    ProQuad - 9 months ProQuad - 11 months ProQuad - 12 months
    Started
    541
    540
    539
    Completed
    524
    474
    461
    Not completed
    17
    66
    78
         Physician decision
             3
             8
             20
         Family moved away
             -
             1
             3
         Allergic reaction to EMLA patch
             -
             -
             1
         Patient in vacation during last visit timeframe
             -
             1
             -
         Adverse event, non-fatal
             2
             -
             1
         Blood sample could not be drawn
             3
             9
             6
         Consent withdrawn by subject
             6
             43
             43
         Lost to follow-up
             3
             4
             4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    ProQuad - 9 months
    Reporting group description
    Subjects received 2 doses of ProQuad (measles, mumps, rubella and varicella (live attenuated)) vaccine: the 1st dose was administered at 9 months of age, and the 2nd dose 90 days later.

    Reporting group title
    ProQuad - 11 months
    Reporting group description
    Subjects received 2 doses of ProQuad (measles, mumps, rubella and varicella (live attenuated)) vaccine: the 1st dose was administered at 11 months of age, and the 2nd dose 90 days later.

    Reporting group title
    ProQuad - 12 months
    Reporting group description
    Subjects received 2 doses of ProQuad (measles, mumps, rubella and varicella (live attenuated)) vaccine: the 1st dose was administered at 12 months of age, and the 2nd dose 90 days later.

    Reporting group values
    ProQuad - 9 months ProQuad - 11 months ProQuad - 12 months Total
    Number of subjects
    541 540 539 1620
    Age categorical
    Units: Subjects
        Infants and toddlers (28 days-23 months)
    541 540 539 1620
    Age continuous
    Age in months at inclusion
    Units: months
        arithmetic mean (standard deviation)
    9.47 ± 0.29 9.48 ± 0.3 9.47 ± 0.3 -
    Gender categorical
    Units: Subjects
        Female
    282 281 258 821
        Male
    259 259 281 799

    End points

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    End points reporting groups
    Reporting group title
    ProQuad - 9 months
    Reporting group description
    Subjects received 2 doses of ProQuad (measles, mumps, rubella and varicella (live attenuated)) vaccine: the 1st dose was administered at 9 months of age, and the 2nd dose 90 days later.

    Reporting group title
    ProQuad - 11 months
    Reporting group description
    Subjects received 2 doses of ProQuad (measles, mumps, rubella and varicella (live attenuated)) vaccine: the 1st dose was administered at 11 months of age, and the 2nd dose 90 days later.

    Reporting group title
    ProQuad - 12 months
    Reporting group description
    Subjects received 2 doses of ProQuad (measles, mumps, rubella and varicella (live attenuated)) vaccine: the 1st dose was administered at 12 months of age, and the 2nd dose 90 days later.

    Primary: #1st# Immunogenicity at 11 vs 12 months of age: Antibody (Ab) response rates to measles, mumps, rubella and varicella 42 days after the 2nd dose of ProQuad

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    End point title
    #1st# Immunogenicity at 11 vs 12 months of age: Antibody (Ab) response rates to measles, mumps, rubella and varicella 42 days after the 2nd dose of ProQuad [1]
    End point description
    Percentage of subjects with an anti-measles Ab titre ≥255 mIU/mL, an anti-mumps Ab titre ≥10.0 ELISA Ab units/mL, an anti-rubella Ab titre ≥10.0 IU/mL, and an anti-varicella Ab titre ≥5 gpELISA units/mL 42 days after injection of the 2nd dose of ProQuad. All Ab titres were measured by Enzyme-Linked Immunosorbent Assay (ELISA), except Ab to varicella determined by glycoprotein ELISA. Analysis was done on the Post-Dose 2 Antigen-specific Per Protocol set (PPS): i.e., all subjects initially seronegative for those antigens (Measles Ab titre <255 mIU/mL, Mumps Ab titre <10.0 ELISA Ab units/mL, Rubella Ab titre <10.0 IU/mL, and Varicella Ab titre <1.25 gpELISA units/mL) and with post-dose immunogenicity evaluation for those antigens. Note: (N=***, ***) represents the number of assessed subjects in the “11 months” and “12 months” groups, respectively.
    End point type
    Primary
    End point timeframe
    42 days after injection of the 2nd dose of ProQuad.
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint corresponds to the 1st primary objective of the study, i.e. comparison of the immunogenicity induced by a 2-dose regimen of ProQuad administered to children of 11 months of age at the time of Dose 1 (arm 2) versus children of 12 months of age at the time of Dose 1 (arm 3), in terms of antibody response rates to measles, mumps, rubella and varicella at Day 42 following Dose 2.
    End point values
    ProQuad - 11 months ProQuad - 12 months
    Number of subjects analysed
    540
    539
    Units: Percentage of subjects
    number (confidence interval 95%)
        Anti-Measles ≥255 mIU/mL (N= 440, 434)
    98 (96.2 to 99.1)
    98.8 (97.3 to 99.6)
        Anti-Mumps ≥10 ELISA Ab units/mL (N= 436, 414)
    99.5 (98.4 to 99.9)
    99.5 (98.3 to 99.9)
        Anti-Rubella ≥10 IU/mL (N= 445, 443)
    99.3 (98 to 99.9)
    99.5 (98.4 to 99.9)
        Anti-Varicella ≥5 gpELISA (N= 299, 347)
    100 (98.8 to 100)
    100 (98.9 to 100)
    Statistical analysis title
    Non-inferiority for Measles
    Statistical analysis description
    The estimates of the differences between Group 2 (11 months) & Group 3 (12 months) response rates were calculated with their 2-sided 95% confidence interval (CI). If all lower bounds of the 95% CI were greater than the non-inferiority margin, it was concluded that Group 2 response rates were non-inferior to Group 3 response rates. Statistical analysis was based on the Miettinen & Nurminen method using a stratification by country. Analysis was done on the Post-Dose 2 Antigen-specific PPS.
    Comparison groups
    ProQuad - 11 months v ProQuad - 12 months
    Number of subjects included in analysis
    1079
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [2]
    Method
    Parameter type
    Difference in percentages of subjects
    Point estimate
    -0.91
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.82
         upper limit
    0.87
    Notes
    [2] - For Measles: # Post-Dose 2 Antigen-specific PPS, N=440, 434 (Groups 2 & 3) # Response rate based on Ab titre ≥255 mIU/mL # Non-inferiority margin, -5%.
    Statistical analysis title
    Non-inferiority for Mumps
    Statistical analysis description
    The estimates of the differences between Group 2 (11 months) & Group 3 (12 months) response rates were calculated with their 2-sided 95% confidence interval (CI). If all lower bounds of the 95% CI were greater than the non-inferiority margin, it was concluded that Group 2 response rates were non-inferior to Group 3 response rates. Statistical analysis was based on the Miettinen & Nurminen method using a stratification by country. Analysis was done on the Post-Dose 2 Antigen-specific PPS.
    Comparison groups
    ProQuad - 11 months v ProQuad - 12 months
    Number of subjects included in analysis
    1079
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [3]
    Method
    Parameter type
    Difference in percentages of subjects
    Point estimate
    0.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    1.32
    Notes
    [3] - For Mumps: # Post-Dose 2 Antigen-specific PPS, N=436, 414 (Groups 2 & 3) # Response rate based on Ab titre ≥10 ELISA Ab units/mL # Non-inferiority margin, -5%.
    Statistical analysis title
    Non-inferiority for Rubella
    Statistical analysis description
    The estimates of the differences between Group 2 (11 months) & Group 3 (12 months) response rates were calculated with their 2-sided 95% confidence interval (CI). If all lower bounds of the 95% CI were greater than the non-inferiority margin, it was concluded that Group 2 response rates were non-inferior to Group 3 response rates. Statistical analysis was based on the Miettinen & Nurminen method using a stratification by country. Analysis was done on the Post-Dose 2 Antigen-specific PPS.
    Comparison groups
    ProQuad - 12 months v ProQuad - 11 months
    Number of subjects included in analysis
    1079
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [4]
    Method
    Parameter type
    Difference in percentages of subjects
    Point estimate
    -0.22
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.55
         upper limit
    1.03
    Notes
    [4] - For Rubella: # Post-Dose 2 Antigen-specific PPS, N=445, 443 (Groups 2 & 3) # Response rate based on Ab titre ≥10 IU/mL # Non-inferiority margin, -5%.
    Statistical analysis title
    Non-inferiority for Varicella
    Statistical analysis description
    The estimates of the differences between Group 2 (11 months) & Group 3 (12 months) response rates were calculated with their 2-sided 95% confidence interval (CI). If all lower bounds of the 95% CI were greater than the non-inferiority margin, it was concluded that Group 2 response rates were non-inferior to Group 3 response rates. Statistical analysis was based on the Miettinen & Nurminen method using a stratification by country. Analysis was done on the Post-Dose 2 Antigen-specific PPS.
    Comparison groups
    ProQuad - 11 months v ProQuad - 12 months
    Number of subjects included in analysis
    1079
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [5]
    Method
    Parameter type
    Difference in percentages of subjects
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.28
         upper limit
    1.1
    Notes
    [5] - For Varicella: # Post-Dose 2 Antigen-specific PPS, N=299, 347 (Groups 2 & 3) # Response rate based on Ab titre ≥5 gpELISA units/mL # Non-inferiority margin, -10%.

    Primary: #2nd# Immunogenicity at 9 vs 12 months of age: Antibody (Ab) response rates to measles, mumps, rubella and varicella 42 days after the 2nd dose of ProQuad

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    End point title
    #2nd# Immunogenicity at 9 vs 12 months of age: Antibody (Ab) response rates to measles, mumps, rubella and varicella 42 days after the 2nd dose of ProQuad [6]
    End point description
    Percentage of subjects with an anti-measles Ab titre ≥255 mIU/mL, an anti-mumps Ab titre ≥10.0 ELISA Ab units/mL, an anti-rubella Ab titre ≥10.0 IU/mL, and an anti-varicella Ab titre ≥5 gpELISA units/mL 42 days after injection of the 2nd dose of ProQuad. All Ab titres were measured by Enzyme-Linked Immunosorbent Assay (ELISA), except Ab to varicella determined by glycoprotein ELISA. Analysis was done on the Post-Dose 2 Antigen-specific Per Protocol set (PPS): i.e., all subjects initially seronegative for those antigens (Measles Ab titre <255 mIU/mL, Mumps Ab titre <10.0 ELISA Ab units/mL, Rubella Ab titre <10.0 IU/mL, and Varicella Ab titre <1.25 gpELISA units/mL) and with post-dose immunogenicity evaluation for those antigens. Note: (N=***, ***) represents the number of assessed subjects in the “9 months” and “12 months” groups, respectively.
    End point type
    Primary
    End point timeframe
    42 days after injection of the 2nd dose of ProQuad.
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint corresponds to the 2nd primary objective of the study (similar to the 1st one) at 9 months of age (i.e. arm 1 versus arm 3), only assessed if the 1st primary objective was reached.
    End point values
    ProQuad - 9 months ProQuad - 12 months
    Number of subjects analysed
    541
    539
    Units: Percentage of subjects
    number (confidence interval 95%)
        Anti-Measles ≥255 mIU/mL (N= 490, 434)
    94.9 (92.6 to 96.7)
    98.8 (97.3 to 99.6)
        Anti-Mumps ≥10 ELISA Ab units/mL (N= 481, 414)
    99.2 (97.9 to 99.8)
    99.5 (98.3 to 99.9)
        Anti-Rubella ≥10 IU/mL (N= 500, 443)
    99.4 (98.3 to 99.9)
    99.5 (98.4 to 99.9)
        Anti-Varicella ≥5 gpELISA (N= 208, 347)
    100 (98.2 to 100)
    100 (98.9 to 100)
    Statistical analysis title
    Non-inferiority for Measles
    Statistical analysis description
    The estimates of the differences between Group 1 (9 months) & Group 3 (12 months) response rates were calculated with their 2-sided 95% confidence interval (CI). If all lower bounds of the 95% CI were greater than the non-inferiority margin, it was concluded that Group 1 response rates were non-inferior to Group 3 response rates. Statistical analysis was based on the Miettinen & Nurminen method using a stratification by country. Analysis was done on the Post-Dose 2 Antigen-specific PPS.
    Comparison groups
    ProQuad - 9 months v ProQuad - 12 months
    Number of subjects included in analysis
    1080
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [7]
    Method
    Parameter type
    Difference in percentages of subjects
    Point estimate
    -3.97
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.44
         upper limit
    -1.87
    Notes
    [7] - For Measles: # Post-Dose 2 Antigen-specific PPS, N=490, 434 (Groups 1 & 3) # Response rate based on Ab titre ≥255 mIU/mL # Non-inferiority margin, -5%.
    Statistical analysis title
    Non-inferiority for Mumps
    Statistical analysis description
    The estimates of the differences between Group 1 (9 months) & Group 3 (12 months) response rates were calculated with their 2-sided 95% confidence interval (CI). If all lower bounds of the 95% CI were greater than the non-inferiority margin, it was concluded that Group 1 response rates were non-inferior to Group 3 response rates. Statistical analysis was based on the Miettinen & Nurminen method using a stratification by country. Analysis was done on the Post-Dose 2 Antigen-specific PPS.
    Comparison groups
    ProQuad - 9 months v ProQuad - 12 months
    Number of subjects included in analysis
    1080
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [8]
    Method
    Parameter type
    Difference in percentages of subjects
    Point estimate
    -0.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.71
         upper limit
    1.01
    Notes
    [8] - For Mumps: # Post-Dose 2 Antigen-specific PPS, N=481, 414 (Groups 1 & 3) # Response rate based on Ab titre ≥10 ELISA Ab units/mL # Non-inferiority margin, -5%.
    Statistical analysis title
    Non-inferiority for Rubella
    Statistical analysis description
    The estimates of the differences between Group 1 (9 months) & Group 3 (12 months) response rates were calculated with their 2-sided 95% confidence interval (CI). If all lower bounds of the 95% CI were greater than the non-inferiority margin, it was concluded that Group 1 response rates were non-inferior to Group 3 response rates. Statistical analysis was based on the Miettinen & Nurminen method using a stratification by country. Analysis was done on the Post-Dose 2 Antigen-specific PPS.
    Comparison groups
    ProQuad - 9 months v ProQuad - 12 months
    Number of subjects included in analysis
    1080
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [9]
    Method
    Parameter type
    Difference in percentages of subjects
    Point estimate
    -0.15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.34
         upper limit
    1.09
    Notes
    [9] - For Rubella: # Post-Dose 2 Antigen-specific PPS, N=500, 443 (Groups 1 & 3) # Response rate based on Ab titre ≥10 IU/mL # Non-inferiority margin, -5%.
    Statistical analysis title
    Non-inferiority for Varicella
    Statistical analysis description
    The estimates of the differences between Group 1 (9 months) & Group 3 (12 months) response rates were calculated with their 2-sided 95% confidence interval (CI). If all lower bounds of the 95% CI were greater than the non-inferiority margin, it was concluded that Group 1 response rates were non-inferior to Group 3 response rates. Statistical analysis was based on the Miettinen & Nurminen method using a stratification by country. Analysis was done on the Post-Dose 2 Antigen-specific PPS.
    Comparison groups
    ProQuad - 9 months v ProQuad - 12 months
    Number of subjects included in analysis
    1080
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [10]
    Method
    Parameter type
    Difference in percentages of subjects
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.83
         upper limit
    1.1
    Notes
    [10] - For Varicella: # Post-Dose 2 Antigen-specific PPS, N=208, 347 (Groups 1 & 3) # Response rate based on Ab titre ≥5 gpELISA units/mL # Non-inferiority margin, -10%.

    Primary: #3rd# Safety at 9 or 11 vs 12 months of age: Global safety from D0 to D28 after the 1st dose of ProQuad

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    End point title
    #3rd# Safety at 9 or 11 vs 12 months of age: Global safety from D0 to D28 after the 1st dose of ProQuad [11]
    End point description
    Adverse events (AEs) occurring after injection of the 1st dose of ProQuad were recorded as follows. 1/ From D0 to D4: # solicited injection-site adverse reactions (ISRs) (erythema, pain, and swelling), 2/ From D0 to D28: # unsolicited ISRs (including erythema, pain, and swelling from D5 to D28), # numeric values of temperature, # AEs of interest (a/ injection-site rashes of interest, b/ non-injection site rashes of interest (measles-like rash, rubella-like rash, varicella-like rash and zoster-like rash), c/ mumps-like illness), # other systemic AEs. AEs at injection sites were always considered as related to vaccine (ISRs). The investigator had to assess whether systemic AEs were vaccine-related systemic AEs or not. Analysis was done on the Post-Dose 1 Safety set, i.e. all subjects who received at least 1 dose of the study vaccine and who had safety follow-up data following Dose 1.
    End point type
    Primary
    End point timeframe
    From Day 0 (D0) to D28 after injection of the 1st dose of ProQuad.
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No formal hypothesis was tested. Thus, no statistical results are presented here.
    End point values
    ProQuad - 9 months ProQuad - 11 months ProQuad - 12 months
    Number of subjects analysed
    528
    480
    466
    Units: Percentage of subjects
    number (confidence interval 95%)
        At least 1 ISR or systemic AE
    81.3 (77.7 to 84.5)
    81.9 (78.1 to 85.2)
    81.1 (77.3 to 84.6)
        At least 1 ISR or vaccine-related systemic AE
    58.7 (54.4 to 62.9)
    60.8 (56.3 to 65.2)
    63.9 (59.4 to 68.3)
        At least 1 ISR
    40.9 (36.7 to 45.2)
    40.2 (35.8 to 44.7)
    40.8 (36.3 to 45.4)
        At least 1 systemic AE
    72 (67.9 to 75.8)
    71.9 (67.6 to 75.9)
    71.9 (67.6 to 75.9)
        At least 1 vaccine-related systemic AE
    36.9 (32.8 to 41.2)
    37.9 (33.6 to 42.4)
    41.8 (37.3 to 46.5)
    No statistical analyses for this end point

    Primary: #3rd# Safety at 9 or 11 vs 12 months of age: Proportion of subjects reporting injection-site reactions (ISRs) after the 1st dose of ProQuad

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    End point title
    #3rd# Safety at 9 or 11 vs 12 months of age: Proportion of subjects reporting injection-site reactions (ISRs) after the 1st dose of ProQuad [12]
    End point description
    Adverse events at injection sites were always considered as related to vaccine (Injection-Site Reactions (ISRs)). Solicited ISRs were defined as injection-site erythema, injection-site pain and injection-site swelling occurring from Day 0 (D0) to D4 after vaccination. Unsolicited ISRs consisted in all other ISRs, including injection-site erythema, injection-site pain and injection-site swelling starting from D5. Analysis was done on the Post-Dose 1 Safety set, i.e. all subjects who received at least 1 dose of the study vaccine and who had safety follow-up data following Dose 1.
    End point type
    Primary
    End point timeframe
    From Day 0 (D0) to D28 after injection of the 1st dose of ProQuad.
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No formal hypothesis was tested. Thus, no statistical results are presented here.
    End point values
    ProQuad - 9 months ProQuad - 11 months ProQuad - 12 months
    Number of subjects analysed
    528
    480
    466
    Units: Percentage of subjects
    number (confidence interval 95%)
        At least 1 solicited ISR
    21.8 (18.3 to 25.5)
    23.3 (19.6 to 27.4)
    27.7 (23.7 to 32)
        Injection-site erythema
    14.4 (11.5 to 17.7)
    15.4 (12.3 to 19)
    17.2 (13.9 to 20.9)
        Injection-site pain
    11.4 (8.8 to 14.4)
    10.4 (7.8 to 13.5)
    13.7 (10.7 to 17.2)
        Injection-site swelling
    2.3 (1.2 to 3.9)
    4.6 (2.9 to 6.9)
    2.4 (1.2 to 4.2)
        At least 1 unsolicited ISR
    24.8 (21.2 to 28.7)
    23.3 (19.6 to 27.4)
    19.1 (15.6 to 23)
    No statistical analyses for this end point

    Primary: #3rd# Safety at 9 or 11 vs 12 months of age: Proportion of subjects reporting adverse events of interest and temperature ≥39.4°C from D0 to D28 after the 1st dose of ProQuad

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    End point title
    #3rd# Safety at 9 or 11 vs 12 months of age: Proportion of subjects reporting adverse events of interest and temperature ≥39.4°C from D0 to D28 after the 1st dose of ProQuad [13]
    End point description
    Injection-site rashes of interest, non-injection site rashes of interest (measles-like rash, rubella-like rash, varicella-like rash and zoster-like rash), mumps-like illness, and rectal (or equivalent) temperature ≥39.4°C were reported from D0 to D28 after vaccination. Percentage of subjects presenting at least once the considered events are presented here. Analysis was done on the Post-Dose 1 Safety set, i.e. all subjects who received at least 1 dose of the study vaccine and who had safety follow-up data following Dose 1.
    End point type
    Primary
    End point timeframe
    From Day 0 (D0) to D28 after injection of the 1st dose of ProQuad.
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No formal hypothesis was tested. Thus, no statistical results are presented here.
    End point values
    ProQuad - 9 months ProQuad - 11 months ProQuad - 12 months
    Number of subjects analysed
    528
    480
    466
    Units: Percentage of subjects
    number (confidence interval 95%)
        At least 1 injection-site rash of interest
    0.2 (0 to 1.1)
    1.5 (0.6 to 3)
    0.2 (0 to 1.2)
        At least 1 non-injection-site rash of interest
    10.6 (8.1 to 13.6)
    11.7 (8.9 to 14.9)
    14.4 (11.3 to 17.9)
        Measles / Measles-like rash
    4 (2.5 to 6)
    5.8 (3.9 to 8.3)
    6.9 (4.7 to 9.6)
        Rubella / Rubella-like rash
    1.3 (0.5 to 2.7)
    1.9 (0.9 to 3.5)
    1.5 (0.6 to 3.1)
        Varicella / Varicella-like rash
    5.3 (3.6 to 7.6)
    4 (2.4 to 6.1)
    6.4 (4.4 to 9.1)
        Zoster / Zoster-like rash
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
        Mumps / Mumps-like illness
    0 (0 to 0)
    0 (0 to 0)
    0.4 (0.1 to 1.5)
        Temperature ≥39.4°C
    8.8 (6.5 to 11.5)
    10.3 (7.7 to 13.4)
    14.8 (11.7 to 18.4)
    No statistical analyses for this end point

    Primary: #3rd# Safety at 9 or 11 vs 12 months of age: Global safety from D0 to D28 after the 2nd dose of ProQuad

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    End point title
    #3rd# Safety at 9 or 11 vs 12 months of age: Global safety from D0 to D28 after the 2nd dose of ProQuad [14]
    End point description
    Adverse events (AEs) occurring after injection of the 2nd dose of ProQuad were recorded as follows. 1/ From D0 to D4: # solicited injection-site adverse reactions (ISRs) (erythema, pain, and swelling), 2/ From D0 to D28: # unsolicited ISRs (including erythema, pain, and swelling from D5 to D28), # numeric values of temperature, # AEs of interest (a/ injection-site rashes of interest, b/ non-injection site rashes of interest (measles-like rash, rubella-like rash, varicella-like rash and zoster-like rash), c/ mumps-like illness), # other systemic AEs. AEs at injection sites were always considered as related to vaccine (ISRs). The investigator had to assess whether systemic AEs were vaccine-related systemic AEs or not. Analysis was done on the Post-Dose 2 Safety set, i.e. all subjects who received at least 1 dose of the study vaccine and who had safety follow-up data following Dose 2.
    End point type
    Primary
    End point timeframe
    From Day 0 (D0) to D28 after injection of the 2nd dose of ProQuad.
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No formal hypothesis was tested. Thus, no statistical results are presented here.
    End point values
    ProQuad - 9 months ProQuad - 11 months ProQuad - 12 months
    Number of subjects analysed
    524
    474
    462
    Units: Percentage of subjects
    number (confidence interval 95%)
        At least 1 ISR or systemic AE
    72.5 (68.5 to 76.3)
    75.7 (71.6 to 79.5)
    72.7 (68.4 to 76.7)
        At least 1 ISR or vaccine-related systemic AE
    55 (50.6 to 59.3)
    57.8 (53.2 to 62.3)
    54.8 (50.1 to 59.4)
        At least 1 ISR
    43.9 (39.6 to 48.3)
    45.4 (40.8 to 50)
    44.2 (39.6 to 48.8)
        At least 1 systemic AE
    58.6 (54.2 to 62.8)
    57.4 (52.8 to 61.9)
    56.1 (51.4 to 60.6)
        At least 1 vaccine-related systemic AE
    26.5 (22.8 to 30.5)
    24.5 (20.7 to 28.6)
    24.2 (20.4 to 28.4)
    No statistical analyses for this end point

    Primary: #3rd# Safety at 9 or 11 vs 12 months of age: Proportion of subjects reporting injection-site reactions (ISRs) after the 2nd dose of ProQuad

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    End point title
    #3rd# Safety at 9 or 11 vs 12 months of age: Proportion of subjects reporting injection-site reactions (ISRs) after the 2nd dose of ProQuad [15]
    End point description
    Adverse events at injection sites were always considered as related to vaccine (Injection-Site Reactions (ISRs)). Solicited ISRs were defined as injection-site erythema, injection-site pain and injection-site swelling occurring from Day 0 (D0) to D4 after vaccination. Unsolicited ISRs consisted in all other ISRs, including injection-site erythema, injection-site pain and injection-site swelling starting from D5. Analysis was done on the Post-Dose 2 Safety set, i.e. all subjects who received at least 1 dose of the study vaccine and who had safety follow-up data following Dose 2.
    End point type
    Primary
    End point timeframe
    From Day 0 (D0) to D28 after injection of the 2nd dose of ProQuad.
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No formal hypothesis was tested. Thus, no statistical results are presented here.
    End point values
    ProQuad - 9 months ProQuad - 11 months ProQuad - 12 months
    Number of subjects analysed
    524
    474
    462
    Units: Percentage of subjects
    number (confidence interval 95%)
        At least 1 solicited ISR
    43.1 (38.8 to 47.5)
    44.7 (40.2 to 49.3)
    44.2 (39.6 to 48.8)
        Injection-site erythema
    40.8 (36.6 to 45.2)
    40.7 (36.3 to 45.3)
    39 (34.5 to 43.6)
        Injection-site pain
    12.4 (9.7 to 15.5)
    14.8 (11.7 to 18.3)
    15.6 (12.4 to 19.2)
        Injection-site swelling
    16.4 (13.3 to 19.9)
    12.2 (9.4 to 15.5)
    14.5 (11.4 to 18)
        At least 1 unsolicited ISR
    1.9 (0.9 to 3.5)
    4.4 (2.8 to 6.7)
    3.9 (2.3 to 6.1)
    No statistical analyses for this end point

    Primary: #3rd# Safety at 9 or 11 vs 12 months of age: Proportion of subjects reporting adverse events of interest and temperature ≥39.4°C from D0 to D28 after the 2nd dose of ProQuad

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    End point title
    #3rd# Safety at 9 or 11 vs 12 months of age: Proportion of subjects reporting adverse events of interest and temperature ≥39.4°C from D0 to D28 after the 2nd dose of ProQuad [16]
    End point description
    Injection-site rashes of interest, non-injection site rashes of interest (measles-like rash, rubella-like rash, varicella-like rash and zoster-like rash), mumps-like illness, and rectal (or equivalent) temperature ≥39.4°C were reported from D0 to D28 after vaccination. Percentage of subjects presenting at least once the considered events are presented here. Analysis was done on the Post-Dose 2 Safety set, i.e. all subjects who received at least 1 dose of the study vaccine and who had safety follow-up data following Dose 2.
    End point type
    Primary
    End point timeframe
    From Day 0 (D0) to D28 after injection of the 2nd dose of ProQuad.
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No formal hypothesis was tested. Thus, no statistical results are presented here.
    End point values
    ProQuad - 9 months ProQuad - 11 months ProQuad - 12 months
    Number of subjects analysed
    524
    474
    462
    Units: Percentage of subjects
    number (confidence interval 95%)
        At least 1 injection-site rash of interest
    0 (0 to 0)
    0 (0 to 0)
    0.2 (0 to 1.2)
        At least 1 non-injection-site rash of interest
    5.7 (3.9 to 8.1)
    8.4 (6.1 to 11.3)
    6.3 (4.2 to 8.9)
        Measles / Measles-like rash
    2.1 (1.1 to 3.7)
    2.7 (1.5 to 4.6)
    2.8 (1.5 to 4.8)
        Rubella / Rubella-like rash
    1.5 (0.7 to 3)
    1.9 (0.9 to 3.6)
    0.9 (0.2 to 2.2)
        Varicella / Varicella-like rash
    2.1 (1.1 to 3.7)
    3.8 (2.3 to 5.9)
    2.6 (1.3 to 4.5)
        Zoster / Zoster-like rash
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
        Mumps / Mumps-like illness
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
        Temperature ≥39.4°C
    7.7 (5.6 to 10.4)
    10 (7.4 to 13.1)
    7.9 (5.6 to 10.7)
    No statistical analyses for this end point

    Secondary: # Immunogenicity: Antibody (Ab) response rates to measles, mumps, rubella and varicella 42 days after the 1st dose of ProQuad

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    End point title
    # Immunogenicity: Antibody (Ab) response rates to measles, mumps, rubella and varicella 42 days after the 1st dose of ProQuad
    End point description
    Percentage of subjects with an anti-measles Ab titre ≥255 mIU/mL, an anti-mumps Ab titre ≥10.0 ELISA Ab units/mL, an anti-rubella Ab titre ≥10.0 IU/mL, and an anti-varicella Ab titre ≥5 gpELISA units/mL 42 days after injection of the 1st dose of ProQuad. All Ab titres were measured by Enzyme-Linked Immunosorbent Assay (ELISA), except Ab to varicella determined by glycoprotein ELISA. Analysis was done on the Post-Dose 1 Antigen-specific Per Protocol set (PPS): i.e., all subjects initially seronegative for those antigens (Measles Ab titre <255 mIU/mL, Mumps Ab titre <10.0 ELISA Ab units/mL, Rubella Ab titre <10.0 IU/mL, and Varicella Ab titre <1.25 gpELISA units/mL) and with post-dose immunogenicity evaluation for those antigens. Note: (N=***, ***,***) represents the number of assessed subjects in the "9 months", “11 months” and “12 months” groups, respectively.
    End point type
    Secondary
    End point timeframe
    42 days after injection of the 1st dose of ProQuad.
    End point values
    ProQuad - 9 months ProQuad - 11 months ProQuad - 12 months
    Number of subjects analysed
    541
    540
    539
    Units: Percentage of subjects
    number (confidence interval 95%)
        Anti-Measles ≥255 mIU/mL (N= 508, 455, 438)
    72.6 (68.5 to 76.5)
    87.9 (84.6 to 90.8)
    90.2 (87 to 92.8)
        Anti-Mumps ≥10 ELISA Ab units/mL (N= 499, 453, 417
    96.6 (94.6 to 98)
    98.7 (97.1 to 99.5)
    98.3 (96.6 to 99.3)
        Anti-Rubella ≥10 IU/mL (N= 518, 460, 447)
    97.7 (96 to 98.8)
    98.9 (97.5 to 99.6)
    98 (96.2 to 99.1)
        Anti-Varicella ≥5 gpELISA (N= 220, 312, 353)
    95 (91.2 to 97.5)
    97.8 (95.4 to 99.1)
    97.5 (95.2 to 98.8)
    No statistical analyses for this end point

    Secondary: # Immunogenicity: Geometric Mean Titres (GMTs) of anti- measles, anti-mumps, anti-rubella and anti-varicella antibodies (Abs) 42 days after the 2nd dose of ProQuad

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    End point title
    # Immunogenicity: Geometric Mean Titres (GMTs) of anti- measles, anti-mumps, anti-rubella and anti-varicella antibodies (Abs) 42 days after the 2nd dose of ProQuad
    End point description
    Ab titres were measured for measles, mumps and rubella by Enzyme-Linked ImmunoSorbent Assay (ELISA) and for varicella by glycoprotein ELISA (gpELISA), 42 days after injection of the 2nd dose of ProQuad. Analysis was done on the Post-dose 2 Antigen-specific Per Protocol set (PPS): i.e., all subjects initially seronegative for those antigens (Measles Ab titre <255 mIU/mL, Mumps Ab titre <10.0 ELISA Ab units/mL, Rubella Ab titre <10.0 IU/mL, and Varicella Ab titre <1.25 gpELISA units/mL) and with post-dose immunogenicity evaluation for those antigens. Note: (N=***, ***,***) represents the number of assessed subjects in the “9 months”, “11 months” and “12 months” groups, respectively.
    End point type
    Secondary
    End point timeframe
    42 days after injection of the 2nd dose of ProQuad.
    End point values
    ProQuad - 9 months ProQuad - 11 months ProQuad - 12 months
    Number of subjects analysed
    541
    540
    539
    Units: Titres
    geometric mean (confidence interval 95%)
        Anti-Measles GMT (N= 490, 440, 434)
    1817 (1645 to 2006)
    2320 (2129 to 2529)
    2703 (2492 to 2933)
        Anti-Mumps GMT (N= 481, 436, 414)
    157 (147 to 168)
    163 (151 to 175)
    172 (159 to 185)
        Anti-Rubella GMT (N= 500, 445, 443)
    106 (99 to 113)
    116 (109 to 124)
    118 (111 to 126)
        Anti-Varicella GMT (N= 208, 299, 347)
    431 (372 to 500)
    460 (410 to 517)
    515 (466 to 569)
    No statistical analyses for this end point

    Secondary: # Immunogenicity: Geometric Mean Titres (GMTs) of anti- measles, anti-mumps, anti-rubella and anti-varicella antibodies (Abs) 42 days after the 1st dose of ProQuad

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    End point title
    # Immunogenicity: Geometric Mean Titres (GMTs) of anti- measles, anti-mumps, anti-rubella and anti-varicella antibodies (Abs) 42 days after the 1st dose of ProQuad
    End point description
    Ab titres were measured for measles, mumps and rubella by Enzyme-Linked ImmunoSorbent Assay (ELISA) and for varicella by glycoprotein ELISA (gpELISA), 42 days after injection of the 1st dose of ProQuad. Analysis was done on the Post-dose 1 Antigen-specific Per Protocol set (PPS): i.e., all subjects initially seronegative for those antigens (Measles Ab titre <255 mIU/mL, Mumps Ab titre <10.0 ELISA Ab units/mL, Rubella Ab titre <10.0 IU/mL, and Varicella Ab titre <1.25 gpELISA units/mL) and with post-dose immunogenicity evaluation for those antigens. Note: (N=***, ***,***) represents the number of assessed subjects in the “9 months”, “11 months” and “12 months” groups, respectively.
    End point type
    Secondary
    End point timeframe
    42 days after injection of the 1st dose of ProQuad.
    End point values
    ProQuad - 9 months ProQuad - 11 months ProQuad - 12 months
    Number of subjects analysed
    541
    540
    539
    Units: Titres
    geometric mean (confidence interval 95%)
        Anti-Measles GMT (N= 508, 455, 438)
    942 (808 to 1098)
    1977 (1736 to 2252)
    2500 (2199 to 2841)
        Anti-Mumps GMT (N= 499, 453, 417)
    73 (68 to 79)
    91 (84 to 99)
    86 (79 to 93)
        Anti-Rubella GMT (N= 518, 460, 447)
    64 (60 to 70)
    77 (71 to 83)
    81 (75 to 88)
        Anti-Varicella GMT (N= 220, 312, 353)
    15 (13 to 16)
    15 (14 to 16)
    15 (14 to 16)
    No statistical analyses for this end point

    Secondary: # Immunogenicity: Rates of subjects with anti-varicella antibody (Ab) titres ≥1.25 gpELISA units/mL 42 days after each dose of ProQuad

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    End point title
    # Immunogenicity: Rates of subjects with anti-varicella antibody (Ab) titres ≥1.25 gpELISA units/mL 42 days after each dose of ProQuad
    End point description
    Percentage of subjects with an anti-varicella Ab titre ≥1.25 gpELISA units/mL (measured by glycoprotein ELISA) 42 days after injection of the 1st dose and the 2nd dose of ProQuad. Analysis was done on the Full Analysis set (FAS): i.e., all randomised subjects who received at least 1 dose of the study vaccine and with any post-vaccination immunogenicity evaluation. Note: (N=***, ***,***) represents the number of assessed subjects in the “9 months”, “11 months” and “12 months” groups, respectively.
    End point type
    Secondary
    End point timeframe
    42 days after injection of the 1st dose and the 2nd dose of ProQuad.
    End point values
    ProQuad - 9 months ProQuad - 11 months ProQuad - 12 months
    Number of subjects analysed
    541
    540
    539
    Units: Percentage of subjects
    number (confidence interval 95%)
        Post-Dose 1 (N= 523, 474, 458)
    99.8 (98.9 to 100)
    100 (99.2 to 100)
    99.8 (98.8 to 100)
        Post-Dose 2 (N= 521, 469, 459)
    100 (99.3 to 100)
    100 (99.2 to 100)
    100 (99.2 to 100)
    No statistical analyses for this end point

    Secondary: # Safety: Proportion of subjects reporting unsolicited injection-site reactions (ISRs) from D0 to D28 after the 1st dose of ProQuad

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    End point title
    # Safety: Proportion of subjects reporting unsolicited injection-site reactions (ISRs) from D0 to D28 after the 1st dose of ProQuad
    End point description
    Adverse events at injection sites were always considered as related to vaccine (Injection-Site Reactions (ISRs)). Unsolicited ISRs occurring from Day 0 (D0) to D28 after vaccination, including injection-site erythema, injection-site pain and injection-site swelling starting from D5, were reported. Percentage of subjects presenting at least once the considered events are presented here. Analysis was done on the Post-Dose 1 Safety set, i.e. all subjects who received at least 1 dose of the study vaccine and who had safety follow-up data following Dose 1.
    End point type
    Secondary
    End point timeframe
    From Day 0 (D0) to D28 after injection of the 1st dose of ProQuad.
    End point values
    ProQuad - 9 months ProQuad - 11 months ProQuad - 12 months
    Number of subjects analysed
    528
    480
    466
    Units: Percentage of subjects
    number (not applicable)
        At least 1 unsolicited ISR
    24.8
    23.3
    19.1
        Injection-site bruising
    1.3
    1.3
    1.1
        Injection-site eczema
    0.2
    0.2
    0
        Injection-site erythema
    16.7
    16.5
    13.1
        Injection-site haematoma
    1.3
    0.4
    1.5
        Injection-site haemorrhage
    1.7
    1.3
    1.7
        Injection-site induration
    1.1
    0.4
    0.6
        Injection-site irritation
    0
    0.4
    0
        Injection-site mass
    0
    0.2
    0
        Injection-site nodule
    0.2
    0.2
    0
        Injection-site pain
    0.2
    0.4
    0.2
        Injection-site papule
    0.8
    0.2
    0
        Injection-site pruritus
    0.2
    0
    0
        Injection-site rash
    2.7
    4
    2.6
        Injection-site swelling
    3.6
    4.2
    2.8
        Injection-site urticaria
    0
    0.2
    0.2
        Injection-site vesicles
    0.8
    0
    0.6
        Injection-site warmth
    0
    0
    0.2
    No statistical analyses for this end point

    Secondary: # Safety: Proportion of subjects reporting unsolicited injection-site reactions (ISRs) from D0 to D28 after the 2nd dose of ProQuad

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    End point title
    # Safety: Proportion of subjects reporting unsolicited injection-site reactions (ISRs) from D0 to D28 after the 2nd dose of ProQuad
    End point description
    Adverse events at injection sites were always considered as related to vaccine (Injection-Site Reactions (ISRs)). Unsolicited ISRs occurring from Day 0 (D0) to D28 after vaccination, including injection-site erythema, injection-site pain and injection-site swelling starting from D5, were reported. Percentage of subjects presenting at least once the considered events are presented here. Analysis was done on the Post-Dose 2 Safety set, i.e. all subjects who received at least 1 dose of the study vaccine and who had safety follow-up data following Dose 2.
    End point type
    Secondary
    End point timeframe
    From Day 0 (D0) to D28 after injection of the 2nd dose of ProQuad.
    End point values
    ProQuad - 9 months ProQuad - 11 months ProQuad - 12 months
    Number of subjects analysed
    524
    474
    462
    Units: Percentage of subjects
    number (not applicable)
        At least 1 unsolicited ISR
    1.9
    4.4
    3.9
        Injection-site bruising
    0.4
    1.1
    0.6
        Injection-site eczema
    0
    0
    0.2
        Injection-site erythema
    0.6
    0.4
    0
        Injection-site haematoma
    0.4
    0.2
    0.2
        Injection-site haemorrhage
    0.2
    1.1
    0.6
        Injection-site induration
    0.2
    0.2
    0.4
        Injection-site irritation
    0
    0
    0.2
        Injection-site movement impairment
    0
    0
    0.2
        Injection-site papule
    0
    0
    0.4
        Injection-site rash
    0.4
    0.8
    0.6
        Injection-site swelling
    0
    0
    0.2
        Injection-site urticaria
    0
    0.4
    0
        Injection-site vesicles
    0
    0.2
    0
        Injection-site warmth
    0
    0
    0.2
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Unsolicited adverse events (AEs) were collected from D0 to D28 after vaccination with Dose 1 and Dose 2 of ProQuad. Serious AEs were collected from the 1st vaccination to the last visit of the subjects.
    Adverse event reporting additional description
    Analysis of AEs was done on the Post-Dose 1 and Post-Dose 2 Safety sets (i.e., all subjects who received the study vaccine and who had safety follow-up data). None of the serious AEs were assessed as vaccine-related. Non-serious systemic AEs (vaccine-related or not) with vaccine-related AEs incidence >1% are presented below.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    10.0
    Reporting groups
    Reporting group title
    Post-Dose 1 - ProQuad - 9 months
    Reporting group description
    # Subjects received 2 doses of ProQuad vaccine: the 1st dose was administered at 9 months of age, and the 2nd dose 90 days later. # Respectively, 380 (72.0%) subjects reported at least 1 non-serious systemic AE and 195 (36.9%) subjects reported at least 1 vaccine-related non-serious systemic AE within 28 days after dose 1.

    Reporting group title
    Post-Dose 1 - ProQuad - 11 months
    Reporting group description
    # Subjects received 2 doses of ProQuad vaccine: the 1st dose was administered at 11 months of age, and the 2nd dose 90 days later. # Respectively, 345 (71.9%) subjects reported at least 1 non-serious systemic AE and 182 (37.9%) subjects reported at least 1 vaccine-related non-serious systemic AE within 28 days after dose 1.

    Reporting group title
    Post-Dose 1 - ProQuad - 12 months
    Reporting group description
    # Subjects received 2 doses of ProQuad vaccine: the 1st dose was administered at 12 months of age, and the 2nd dose 90 days later. # Respectively, 335 (71.9%) subjects reported at least 1 non-serious systemic AE and 195 (41.8%) subjects reported at least 1 vaccine-related non-serious systemic AE within 28 days after dose 1.

    Reporting group title
    Post-Dose 2 - ProQuad - 9 months
    Reporting group description
    # Subjects received 2 doses of ProQuad vaccine: the 1st dose was administered at 9 months of age, and the 2nd dose 90 days later. # Respectively, 307 (58.6%) subjects reported at least 1 non-serious systemic AE and 139 (26.5%) subjects reported at least 1 vaccine-related non-serious systemic AE within 28 days after dose 2.

    Reporting group title
    Post-Dose 2 - ProQuad - 11 months
    Reporting group description
    # Subjects received 2 doses of ProQuad vaccine: the 1st dose was administered at 11 months of age, and the 2nd dose 90 days later. # Respectively, 272 (57.4%) subjects reported at least 1 non-serious systemic AE and 116 (24.5%) subjects reported at least 1 vaccine-related non-serious systemic AE within 28 days after dose 2.

    Reporting group title
    Post-Dose 2 - ProQuad - 12 months
    Reporting group description
    # Subjects received 2 doses of ProQuad vaccine: the 1st dose was administered at 12 months of age, and the 2nd dose 90 days later. # Respectively, 259 (56.1%) subjects reported at least 1 non-serious systemic AE and 112 (24.2%) subjects reported at least 1 vaccine-related non-serious systemic AE within 28 days after dose 2.

    Serious adverse events
    Post-Dose 1 - ProQuad - 9 months Post-Dose 1 - ProQuad - 11 months Post-Dose 1 - ProQuad - 12 months Post-Dose 2 - ProQuad - 9 months Post-Dose 2 - ProQuad - 11 months Post-Dose 2 - ProQuad - 12 months
    Total subjects affected by serious adverse events
         subjects affected / exposed
    18 / 528 (3.41%)
    8 / 480 (1.67%)
    8 / 466 (1.72%)
    3 / 524 (0.57%)
    6 / 474 (1.27%)
    1 / 462 (0.22%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 480 (0.21%)
    3 / 466 (0.64%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Forearm fracture
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 480 (0.21%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    1 / 462 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile convulsion
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 480 (0.21%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchiolitis
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 480 (0.00%)
    1 / 466 (0.21%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 528 (0.19%)
    2 / 480 (0.42%)
    2 / 466 (0.43%)
    1 / 524 (0.19%)
    2 / 474 (0.42%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 480 (0.00%)
    1 / 466 (0.21%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Exanthema subitum
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    1 / 524 (0.19%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    3 / 528 (0.57%)
    3 / 480 (0.63%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis adenovirus
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    1 / 524 (0.19%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis Norwalk virus
         subjects affected / exposed
    2 / 528 (0.38%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    6 / 528 (1.14%)
    0 / 480 (0.00%)
    1 / 466 (0.21%)
    0 / 524 (0.00%)
    1 / 474 (0.21%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    1 / 474 (0.21%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngitis
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 480 (0.21%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 480 (0.00%)
    1 / 466 (0.21%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media acute
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 480 (0.21%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 480 (0.21%)
    1 / 466 (0.21%)
    0 / 524 (0.00%)
    1 / 474 (0.21%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    1 / 474 (0.21%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 480 (0.21%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 480 (0.00%)
    0 / 466 (0.00%)
    0 / 524 (0.00%)
    0 / 474 (0.00%)
    0 / 462 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    Post-Dose 1 - ProQuad - 9 months Post-Dose 1 - ProQuad - 11 months Post-Dose 1 - ProQuad - 12 months Post-Dose 2 - ProQuad - 9 months Post-Dose 2 - ProQuad - 11 months Post-Dose 2 - ProQuad - 12 months
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    380 / 528 (71.97%)
    345 / 480 (71.88%)
    335 / 466 (71.89%)
    307 / 524 (58.59%)
    272 / 474 (57.38%)
    259 / 462 (56.06%)
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    42 / 528 (7.95%)
    36 / 480 (7.50%)
    27 / 466 (5.79%)
    23 / 524 (4.39%)
    12 / 474 (2.53%)
    15 / 462 (3.25%)
         occurrences all number
    43
    39
    29
    25
    13
    15
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    4 / 528 (0.76%)
    7 / 480 (1.46%)
    13 / 466 (2.79%)
    5 / 524 (0.95%)
    3 / 474 (0.63%)
    3 / 462 (0.65%)
         occurrences all number
    4
    8
    14
    6
    3
    3
    Irritability
         subjects affected / exposed
    52 / 528 (9.85%)
    56 / 480 (11.67%)
    68 / 466 (14.59%)
    39 / 524 (7.44%)
    24 / 474 (5.06%)
    29 / 462 (6.28%)
         occurrences all number
    74
    77
    79
    53
    26
    34
    Pyrexia
         subjects affected / exposed
    58 / 528 (10.98%)
    68 / 480 (14.17%)
    60 / 466 (12.88%)
    39 / 524 (7.44%)
    38 / 474 (8.02%)
    27 / 462 (5.84%)
         occurrences all number
    70
    87
    70
    47
    46
    29
    Psychiatric disorders
    Crying
         subjects affected / exposed
    24 / 528 (4.55%)
    12 / 480 (2.50%)
    10 / 466 (2.15%)
    15 / 524 (2.86%)
    7 / 474 (1.48%)
    11 / 462 (2.38%)
         occurrences all number
    26
    20
    12
    17
    9
    15
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    46 / 528 (8.71%)
    46 / 480 (9.58%)
    45 / 466 (9.66%)
    22 / 524 (4.20%)
    24 / 474 (5.06%)
    20 / 462 (4.33%)
         occurrences all number
    49
    53
    50
    22
    24
    22
    Vomiting
         subjects affected / exposed
    25 / 528 (4.73%)
    17 / 480 (3.54%)
    18 / 466 (3.86%)
    15 / 524 (2.86%)
    11 / 474 (2.32%)
    8 / 462 (1.73%)
         occurrences all number
    28
    19
    19
    16
    12
    9
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    6 / 528 (1.14%)
    17 / 480 (3.54%)
    15 / 466 (3.22%)
    15 / 524 (2.86%)
    7 / 474 (1.48%)
    7 / 462 (1.52%)
         occurrences all number
    7
    19
    16
    17
    7
    8
    Rash
         subjects affected / exposed
    30 / 528 (5.68%)
    26 / 480 (5.42%)
    26 / 466 (5.58%)
    29 / 524 (5.53%)
    16 / 474 (3.38%)
    18 / 462 (3.90%)
         occurrences all number
    35
    30
    29
    29
    16
    19
    Rash morbilliform
         subjects affected / exposed
    21 / 528 (3.98%)
    28 / 480 (5.83%)
    32 / 466 (6.87%)
    11 / 524 (2.10%)
    13 / 474 (2.74%)
    13 / 462 (2.81%)
         occurrences all number
    22
    28
    32
    11
    13
    13
    Rash rubelliform
         subjects affected / exposed
    7 / 528 (1.33%)
    9 / 480 (1.88%)
    7 / 466 (1.50%)
    8 / 524 (1.53%)
    9 / 474 (1.90%)
    4 / 462 (0.87%)
         occurrences all number
    7
    9
    8
    9
    9
    4
    Rash vesicular
         subjects affected / exposed
    28 / 528 (5.30%)
    19 / 480 (3.96%)
    30 / 466 (6.44%)
    11 / 524 (2.10%)
    18 / 474 (3.80%)
    12 / 462 (2.60%)
         occurrences all number
    28
    22
    30
    11
    18
    13
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    15 / 528 (2.84%)
    2 / 480 (0.42%)
    12 / 466 (2.58%)
    3 / 524 (0.57%)
    0 / 474 (0.00%)
    1 / 462 (0.22%)
         occurrences all number
    15
    2
    13
    4
    0
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    38 / 528 (7.20%)
    22 / 480 (4.58%)
    18 / 466 (3.86%)
    18 / 524 (3.44%)
    25 / 474 (5.27%)
    21 / 462 (4.55%)
         occurrences all number
    40
    24
    19
    19
    27
    23
    Otitis media
         subjects affected / exposed
    28 / 528 (5.30%)
    27 / 480 (5.63%)
    18 / 466 (3.86%)
    20 / 524 (3.82%)
    21 / 474 (4.43%)
    25 / 462 (5.41%)
         occurrences all number
    33
    28
    20
    20
    22
    28
    Rhinitis
         subjects affected / exposed
    64 / 528 (12.12%)
    67 / 480 (13.96%)
    43 / 466 (9.23%)
    49 / 524 (9.35%)
    35 / 474 (7.38%)
    47 / 462 (10.17%)
         occurrences all number
    75
    70
    49
    52
    39
    50
    Upper respiratory tract infection
         subjects affected / exposed
    40 / 528 (7.58%)
    34 / 480 (7.08%)
    29 / 466 (6.22%)
    36 / 524 (6.87%)
    45 / 474 (9.49%)
    59 / 462 (12.77%)
         occurrences all number
    45
    35
    34
    40
    52
    64

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    31 Aug 2007
    Protocol amendment applicable only to France, made to answer the demand of the French Competent Authorities (AFSSAPS). Addition of a special warning in order for the investigators to perform a supervision after vaccination and to have an appropriate medical treatment readily available in case of a rare anaphylactic reaction following the administration of the vaccine.
    15 Feb 2008
    # Implementation of Protocol amendment 1 in Finland and Germany. # Update of logistics and study timelines. # Correction of some typos.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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