Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase III Observer-Blind, Randomized, Controlled, Multicenter Study to Evaluate Safety, Tolerability, and Immunogenicity of Two Trivalent Subunit Inactivated Influenza Vaccines (Agrippal and Fluvirin) in Healthy Children Aged 3 to 8 years, in Healthy Children/Adolescents Aged 9 to 17 Years And in Healthy Adults Aged 18 to 64 Years

    Summary
    EudraCT number
    		 2014-004757-14
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    20 Dec 2007

    Results information
    Results version number
    		 v2(current)
    This version publication date
    28 Jul 2016
    First version publication date
    04 Feb 2015
    Other versions
    		 v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    Required for the re-QC because of EudraCT system glitch as possible updates to results are required. Moreover, the study is now transferred to another primary user.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    V71P5
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00464672
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Vaccines and Diagnostics S.r.l.
    Sponsor organisation address
    Via Fiorentina, 1, Siena, Italy, 53100
    Public contact
    Posting Director, Novartis Vaccines , RegistryContactVaccinesUS@novartis.com
    Scientific contact
    Posting Director, Novartis Vaccines , RegistryContactVaccinesUS@novartis.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
    06 Mar 2008
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Dec 2007
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate immunogenicity, measured by seroprotection (percentage of subjects achieving a hemagglutination inhibition [HI] titer ≥40) and by percentage of subjects achieving seroconversion (defined as negative pre-vaccination serum [HI<10]/post-vaccination HI titer ≥40) or significant increase (defined as at least a 4-fold increase in titer from non-negative prevaccination serum [HI≥10]), of one injection of Agrippal, administered to healthy adults aged 18 to 64 years according to the CBER Guidance for Industry issued in May 2007. To evaluate safety and tolerability of one injection of either Agrippal or Fluvirin, administered to adults aged 18 to 64 years and Children/adolescents aged 9 to 17 years and two injections of either Agrippal or Fluvirin, administered 4 weeks apart to healthy children aged 3 to 8 years.
    Protection of trial subjects
    This trial was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with Good Clinical Practices (GCPs) and the applicable regulatory requirement(s) for the country in which the trial was conducted, GCP according to International Conference on Harmonisation (ICH) guidelines, and applicable Standard Operating Procedures (SOPs).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    11 Apr 2007
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 6 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 1893
    Worldwide total number of subjects
    1893
    EEA total number of subjects
    0
    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)
    0
    Children (2-11 years)
    824
    Adolescents (12-17 years)
    376
    Adults (18-64 years)
    691
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects were enrolled at 2 study centers in Argentina.

    Pre-assignment
    Screening details
    		 All enrolled subjects were included in the trial.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Influenza Virus Vaccine (18 to 64 Years)
    Arm description
    		 One injection of the investigational influenza virus vaccine was administered intramuscularly.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Trivalent influenza virus vaccine (surface antigen, inactivated, egg-derived)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One 0.5 mL IM injection, in the deltoid muscle, preferably of the non-dominant arm.

    Arm title
    		 Comparator Influenza Vaccine (18 to 64 Years)
    Arm description
    		 One injection of the comparator influenza vaccine was administered intramuscularly.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Trivalent influenza virus vaccine (surface antigen, inactivated, egg-derived, Fluvirin platform)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One 0.5 mL IM injection, in the deltoid muscle, preferably of the non-dominant arm.

    Arm title
    		 Influenza Virus Vaccine (9 to 17 Years)
    Arm description
    		 One injection of the investigational influenza virus vaccine was administered intramuscularly.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Trivalent influenza virus vaccine (surface antigen, inactivated, egg-derived)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One 0.5 mL IM injection, in the deltoid muscle, preferably of the non-dominant arm.

    Arm title
    		 Comparator Influenza Vaccine (9 to 17 Years)
    Arm description
    		 One injection of the comparator influenza vaccine was administered intramuscularly
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Trivalent influenza virus vaccine (surface antigen, inactivated, egg-derived, Fluvirin platform)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One 0.5 mL IM injection, in the deltoid muscle, preferably of the non-dominant arm.

    Arm title
    		 Influenza Virus Vaccine (3 to 8 Years)
    Arm description
    		 Two injections of the investigational influenza virus vaccine were administered intramuscularly.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Trivalent influenza virus vaccine (surface antigen, inactivated, egg-derived)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Two 0.5 mL intramuscular (IM) injections administered 4 weeks apart, in the deltoid muscle, preferably of the non-dominant arm.

    Arm title
    		 Comparator Influenza Vaccine (3 to 8 Years)
    Arm description
    		 Two injections of the comparator influenza vaccine were administered intramuscularly.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Trivalent influenza virus vaccine (surface antigen, inactivated, egg-derived, Fluvirin platform)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Two 0.5 mL intramuscular (IM) injections administered 4 weeks apart, in the deltoid muscle, preferably of the non-dominant arm.

    Number of subjects in period 1
    		Influenza Virus Vaccine (18 to 64 Years) Comparator Influenza Vaccine (18 to 64 Years) Influenza Virus Vaccine (9 to 17 Years) Comparator Influenza Vaccine (9 to 17 Years) Influenza Virus Vaccine (3 to 8 Years) Comparator Influenza Vaccine (3 to 8 Years)
    Started
    460
    232
    400
    200
    402
    199
    Completed
    435
    222
    400
    199
    392
    195
    Not completed
    25
    10
    0
    1
    10
    4
         Consent withdrawn by subject
    -
    -
    -
    1
    9
    4
         Lost to follow-up
    25
    10
    -
    -
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Influenza Virus Vaccine (18 to 64 Years)
    Reporting group description
    		 One injection of the investigational influenza virus vaccine was administered intramuscularly.

    Reporting group title
    Comparator Influenza Vaccine (18 to 64 Years)
    Reporting group description
    		 One injection of the comparator influenza vaccine was administered intramuscularly.

    Reporting group title
    Influenza Virus Vaccine (9 to 17 Years)
    Reporting group description
    		 One injection of the investigational influenza virus vaccine was administered intramuscularly.

    Reporting group title
    Comparator Influenza Vaccine (9 to 17 Years)
    Reporting group description
    		 One injection of the comparator influenza vaccine was administered intramuscularly

    Reporting group title
    Influenza Virus Vaccine (3 to 8 Years)
    Reporting group description
    		 Two injections of the investigational influenza virus vaccine were administered intramuscularly.

    Reporting group title
    Comparator Influenza Vaccine (3 to 8 Years)
    Reporting group description
    		 Two injections of the comparator influenza vaccine were administered intramuscularly.

    Reporting group values
    		 Influenza Virus Vaccine (18 to 64 Years) Comparator Influenza Vaccine (18 to 64 Years) Influenza Virus Vaccine (9 to 17 Years) Comparator Influenza Vaccine (9 to 17 Years) Influenza Virus Vaccine (3 to 8 Years) Comparator Influenza Vaccine (3 to 8 Years) Total
    Number of subjects
    		 460 232 400 200 402 199 1893
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 149 74 402 199 824
        Adolescents (12-17 years)
    		 0 0 251 125 0 0 376
        Adults (18-64 years)
    		 458 232 0 1 0 0 691
        From 65-84 years
    		 2 0 0 0 0 0 2
        85 years and over
    		 0 0 0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 38.8 ± 12.4 37.8 ± 12.6 12.7 ± 2.6 12.8 ± 2.6 5.5 ± 1.7 5.4 ± 1.7 -
    Gender categorical
    Units: Subjects
        Female
    		 293 130 222 109 172 98 1024
        Male
    		 167 102 178 91 230 101 869

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Influenza Virus Vaccine (18 to 64 Years)
    Reporting group description
    		 One injection of the investigational influenza virus vaccine was administered intramuscularly.

    Reporting group title
    Comparator Influenza Vaccine (18 to 64 Years)
    Reporting group description
    		 One injection of the comparator influenza vaccine was administered intramuscularly.

    Reporting group title
    Influenza Virus Vaccine (9 to 17 Years)
    Reporting group description
    		 One injection of the investigational influenza virus vaccine was administered intramuscularly.

    Reporting group title
    Comparator Influenza Vaccine (9 to 17 Years)
    Reporting group description
    		 One injection of the comparator influenza vaccine was administered intramuscularly

    Reporting group title
    Influenza Virus Vaccine (3 to 8 Years)
    Reporting group description
    		 Two injections of the investigational influenza virus vaccine were administered intramuscularly.

    Reporting group title
    Comparator Influenza Vaccine (3 to 8 Years)
    Reporting group description
    		 Two injections of the comparator influenza vaccine were administered intramuscularly.

    Subject analysis set title
    Agrippal-Enrolled Population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All subjects who had data in the DEMOG panel.

    Subject analysis set title
    Fluvirin-Enrolled Population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All subjects who had data in the DEMOG panel.

    Subject analysis set title
    Agrippal - MITT Population
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    All randomized subjects in the enrolled population who received a study vaccination, and provided at least one evaluable serum sample.

    Subject analysis set title
    Fluvirin - MITT Population
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    All randomized subjects in the enrolled population who received a study vaccination, and provided at least one evaluable serum sample.

    Subject analysis set title
    Agrippal - Per-Protocol Population
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All subjects in the Full Analysis Set/MITT population who received all the relevant doses of vaccine correctly, and provided evaluable serum samples at the relevant time points, and had no major protocol deviation

    Subject analysis set title
    Fluvirin - Per-Protocol Population
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All subjects in the Full Analysis Set/MITT population who received all the relevant doses of vaccine correctly, and provided evaluable serum samples at the relevant time points, and had no major protocol deviation.

    Subject analysis set title
    Agrippal - Safety Population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the Exposed population who provided post-baseline safety data.

    Subject analysis set title
    Fluvirin - Safety Population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects in the Exposed population who provided post-baseline safety data.

    Primary: Percentage of Subjects With Seroprotection, in Healthy Adults 18 to 64 Years of Age

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Seroprotection, in Healthy Adults 18 to 64 Years of Age [1] [2]
    End point description
    To evaluate immunogenicity, measured by seroprotection (percentage of subjects achieving a hemagglutination inhibition [HI] titer ≥40) after one injection of the investigational influenza virus vaccine, administered to healthy adults 18 to 64 years of age. The CBER Guidance states that the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroprotection meet or exceed 70%.
    End point type
    Primary
    End point timeframe
    21 days after vaccination
    Notes
    [1] - 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: There were no statistical analysis done.
    [2] - 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: There were no statistical analysis done.
    End point values
    		 Influenza Virus Vaccine (18 to 64 Years) Comparator Influenza Vaccine (18 to 64 Years)
    Number of subjects analysed
    424
    219
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Strain A/H1N1
    93 (90 to 95)
    99 (97 to 100)
        Strain A/H3N2
    96 (94 to 98)
    100 (98 to 100)
        Strain B
    91 (87 to 93)
    86 (81 to 91)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Achieving a Seroconversion Rate, in Adults 18 to 64 Years of Age

    		 Close Top of page
    End point title
    		 Percentage of Subjects Achieving a Seroconversion Rate, in Adults 18 to 64 Years of Age [3] [4]
    End point description
    Seroconversion rate is defined as percentage of subjects achieving seroconversion (defined as negative pre-vaccination serum [HI<10]/ post-vaccination HI titer ≥40) or significant increase defined as at least a 4-fold increase). According to the CBER Guidance, the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion/significant increase meets or exceeds 40%.
    End point type
    Primary
    End point timeframe
    21 days after vaccination
    Notes
    [3] - 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: There were no statistical analysis done.
    [4] - 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: There were no statistical analysis done.
    End point values
    		 Influenza Virus Vaccine (18 to 64 Years) Comparator Influenza Vaccine (18 to 64 Years)
    Number of subjects analysed
    424
    219
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Strain A/H1N1
    74 (69 to 78)
    86 (81 to 90)
        Strain A/H3N2
    72 (68 to 76)
    89 (84 to 92)
        Strain B
    77 (72 to 81)
    74 (68 to 80)
    No statistical analyses for this end point

    Secondary: Number of Subjects Reporting Solicited Local and Systemic Symptoms in Adults 18 to 64 Years of Age

    		 Close Top of page
    End point title
    		 Number of Subjects Reporting Solicited Local and Systemic Symptoms in Adults 18 to 64 Years of Age [5]
    End point description
    Solicited local and systemic reactions were assessed after vaccination in adults 18 to 64 years of age.
    End point type
    Secondary
    End point timeframe
    7 days after vaccination
    Notes
    [5] - 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: There were no statistical analysis done.
    End point values
    		 Influenza Virus Vaccine (18 to 64 Years) Comparator Influenza Vaccine (18 to 64 Years)
    Number of subjects analysed
    460
    232 [6]
    Units: Number of Subjects
        Any local reaction
    161
    89
        Erythema
    27
    12
        Induration
    38
    24
        Swelling
    29
    15
        Ecchymosis
    24
    15
        Pain
    117
    70
        Any Systemic Reaction
    147
    84
        Chills
    21
    17
        Malaise
    55
    27
        Myalgia
    66
    37
        Arthralgia
    30
    14
        Headache
    108
    42
        Sweating
    24
    11
        Fatigue
    46
    24
        Fever
    10
    6
    Notes
    [6] - Actual number of subjects analysed are 233 as one subject was mistakenly enrolled in this age strata
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Seroprotection, in Healthy Children/Adolescents 9 to 17 Years of Age

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Seroprotection, in Healthy Children/Adolescents 9 to 17 Years of Age [7]
    End point description
    To descriptively evaluate immunogenicity, measured by seroprotection rate (percentage of subjects achieving a hemagglutination inhibition [HI] titer ≥40) after one injection of investigational influenza virus vaccine, administered to healthy children/adolescents 9 to 17 years of age.
    End point type
    Secondary
    End point timeframe
    21 days after vaccination
    Notes
    [7] - 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: There were no statistical analysis done.
    End point values
    		 Influenza Virus Vaccine (9 to 17 Years) Comparator Influenza Vaccine (9 to 17 Years)
    Number of subjects analysed
    393
    192
    Units: Percentages of subjects
    number (confidence interval 95%)
        Strain A/H1N1
    99 (97 to 100)
    98 (96 to 100)
        Strain A/H3N2
    100 (99 to 100)
    100 (98 to 100)
        Strain B
    93 (90 to 95)
    89 (84 to 93)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving Seroconversion Rate, in Healthy Children/Adolescents 9 to 17 Years of Age

    		 Close Top of page
    End point title
    		 Percentage of Subjects Achieving Seroconversion Rate, in Healthy Children/Adolescents 9 to 17 Years of Age [8]
    End point description
    Seroconversion rate is defined as percentage of subjects achieving seroconversion (defined as negative pre-vaccination serum [HI<10]/ post-vaccination HI titer ≥40) or significant increase (defined as at least a 4-fold increase) after one injection of the investigational influenza virus vaccine, administered to healthy children/adolescents 9 to 17 years of age.
    End point type
    Secondary
    End point timeframe
    21 days after vaccination
    Notes
    [8] - 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: There were no statistical analysis done.
    End point values
    		 Influenza Virus Vaccine (9 to 17 Years) Comparator Influenza Vaccine (9 to 17 Years)
    Number of subjects analysed
    393
    192
    Units: Percentage of subjects
    number (confidence interval 95%)
        Strain A/H1N1
    92 (88 to 94)
    91 (86 to 94)
        Strain A/H3N2
    67 (62 to 72)
    92 (87 to 95)
        Strain B
    81 (76 to 84)
    73 (67 to 80)
    No statistical analyses for this end point

    Secondary: Geometric Mean Titers (GMTs), in Healthy Children/Adolescents 9 to 17 Years of Age

    		 Close Top of page
    End point title
    		 Geometric Mean Titers (GMTs), in Healthy Children/Adolescents 9 to 17 Years of Age [9]
    End point description
    To evaluate immunogenicity measured by GMTs after one injection of investigational influenza virus vaccine, administered to healthy children/adolescents 9 to 17 years of age.
    End point type
    Secondary
    End point timeframe
    21 days after vaccination
    Notes
    [9] - 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: There were no statistical analysis done.
    End point values
    		 Influenza Virus Vaccine (9 to 17 Years) Comparator Influenza Vaccine (9 to 17 Years)
    Number of subjects analysed
    393
    192
    Units: Titers
    geometric mean (confidence interval 95%)
        Strain A/H1N1
    960 (857 to 1076)
    1246 (1058 to 1467)
        Strain A/H3N2
    493 (453 to 536)
    1463 (1296 to 1651)
        Strain B
    144 (127 to 163)
    114 (95 to 136)
    No statistical analyses for this end point

    Secondary: Number of Subjects Reporting Solicited Local and Systemic Symptoms in Children/Adolescents 9 to 17 Years of Age

    		 Close Top of page
    End point title
    		 Number of Subjects Reporting Solicited Local and Systemic Symptoms in Children/Adolescents 9 to 17 Years of Age [10]
    End point description
    Solicited local and systemic reactions were assessed after vaccination in children/adolescents 9 to 17 years of age.
    End point type
    Secondary
    End point timeframe
    7 days after vaccination
    Notes
    [10] - 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: There were no statistical analysis done.
    End point values
    		 Influenza Virus Vaccine (9 to 17 Years) Comparator Influenza Vaccine (9 to 17 Years)
    Number of subjects analysed
    400
    199
    Units: Number of Subjects
        Any local reaction
    134
    62
        Erythema
    7
    3
        Induration
    28
    13
        Swelling
    28
    14
        Ecchymosis
    9
    1
        Pain
    117
    58
        Any Systemic reaction
    91
    49
        Chills
    18
    11
        Malaise
    18
    8
        Myalgia
    35
    25
        Arthralgia
    11
    5
        Headache
    52
    22
        Sweating
    4
    3
        Fatigue
    25
    9
        Fever
    1
    4
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Seroprotection, in Healthy Children 3 to 8 years Age

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Seroprotection, in Healthy Children 3 to 8 years Age [11]
    End point description
    To descriptively evaluate immunogenicity, measured by seroprotection rate (percentage of subjects achieving a hemagglutination inhibition [HI] titer ≥40) after two injections of the investigational influenza virus vaccine, in healthy children 3 to 8 years of age.
    End point type
    Secondary
    End point timeframe
    50 days after vaccination
    Notes
    [11] - 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: There were no statistical analysis done.
    End point values
    		 Influenza Virus Vaccine (3 to 8 Years) Comparator Influenza Vaccine (3 to 8 Years)
    Number of subjects analysed
    296
    149
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Strain A/H1N1
    97 (94 to 99)
    99 (95 to 100)
        Strain A/H3N2
    100 (99 to 100)
    99 (96 to 100)
        Strain B
    85 (80 to 89)
    81 (73 to 87)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving Seroconversion Rate, in Healthy Children 3 to 8 Years of Age

    		 Close Top of page
    End point title
    		 Percentage of Subjects Achieving Seroconversion Rate, in Healthy Children 3 to 8 Years of Age [12]
    End point description
    Seroconversion rate is defined as percentage of subjects achieving seroconversion (defined as negative pre-vaccination serum [HI<10]/ post-vaccination HI titer ≥40) or significant increase (defined as at least a 4-fold increase) after two injections of the investigational influenza virus vaccine, in healthy children 3 to 8 years of age.
    End point type
    Secondary
    End point timeframe
    50 days after vaccination
    Notes
    [12] - 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: There were no statistical analysis done.
    End point values
    		 Influenza Virus Vaccine (3 to 8 Years) Comparator Influenza Vaccine (3 to 8 Years)
    Number of subjects analysed
    296
    149
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Strain A/H1N1
    95 (91 to 97)
    97 (92 to 99)
        Strain A/H3N2
    86 (82 to 90)
    95 (90 to 98)
        Strain B
    83 (78 to 87)
    79 (72 to 85)
    No statistical analyses for this end point

    Secondary: Geometric Mean Titers (GMTs), in Healthy Children 3 to 8 Years of Age

    		 Close Top of page
    End point title
    		 Geometric Mean Titers (GMTs), in Healthy Children 3 to 8 Years of Age [13]
    End point description
    To evaluate immunogenicity measured by GMTs after two injections of the investigational influenza virus vaccine, in healthy children 3 to 8 years of age.
    End point type
    Secondary
    End point timeframe
    50 days after vaccination
    Notes
    [13] - 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: There were no statistical analysis done.
    End point values
    		 Influenza Virus Vaccine (3 to 8 Years) Comparator Influenza Vaccine (3 to 8 Years)
    Number of subjects analysed
    296
    149
    Units: Titers
    geometric mean (confidence interval 95%)
        Strain A/H1N1
    625 (532 to 734)
    716 (570 to 898)
        Strain A/H3N2
    710 (637 to 792)
    1472 (1263 to 1715)
        Strain B
    157 (133 to 185)
    126 (100 to 158)
    No statistical analyses for this end point

    Secondary: Number of Subjects Reporting Solicited Local and Systemic Symptoms after 1st vaccination in Children 3 to 8 Years of Age

    		 Close Top of page
    End point title
    		 Number of Subjects Reporting Solicited Local and Systemic Symptoms after 1st vaccination in Children 3 to 8 Years of Age [14]
    End point description
    Solicited local and systemic reactions were assessed after 1st injection in children 3 to 8 years of age.
    End point type
    Secondary
    End point timeframe
    7 days after 1st Vaccination
    Notes
    [14] - 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: There were no statistical analysis done.
    End point values
    		 Influenza Virus Vaccine (3 to 8 Years) Comparator Influenza Vaccine (3 to 8 Years)
    Number of subjects analysed
    402
    199
    Units: Number of Subjects
        Any Local Reaction
    92
    56
        Erythema
    9
    5
        Induration
    11
    10
        Swelling
    22
    16
        Ecchymosis
    18
    9
        Pain
    68
    40
        Any Systemic Reaction
    66
    38
        Chills
    10
    8
        Malaise
    21
    12
        Myalgia
    19
    9
        Arthralgia
    5
    2
        Headache
    28
    18
        Sweating
    5
    3
        Fatigue
    18
    9
        Fever
    12
    3
    No statistical analyses for this end point

    Secondary: Number of Subjects Reporting Solicited Local and Systemic Symptoms after 2nd vaccination in Children 3 to 8 Years of Age

    		 Close Top of page
    End point title
    		 Number of Subjects Reporting Solicited Local and Systemic Symptoms after 2nd vaccination in Children 3 to 8 Years of Age [15]
    End point description
    Solicited local and systemic reactions were assessed after 2nd vaccination in children 3 to 8 years of age.
    End point type
    Secondary
    End point timeframe
    7 days after 2nd Vaccination
    Notes
    [15] - 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: There were no statistical analysis done.
    End point values
    		 Influenza Virus Vaccine (3 to 8 Years) Comparator Influenza Vaccine (3 to 8 Years)
    Number of subjects analysed
    396
    197
    Units: Number of Subjects
        Any Local Reaction
    66
    39
        Erythema
    3
    3
        Induration
    13
    8
        Swelling
    13
    8
        Ecchymosis
    10
    5
        Pain
    57
    35
        Any Systemic Reaction
    41
    21
        Chills
    8
    5
        Malaise
    19
    7
        Myalgia
    19
    10
        Arthralgia
    5
    1
        Headache
    15
    11
        Sweating
    3
    1
        Fatigue
    10
    4
        Fever
    10
    5
    No statistical analyses for this end point

    Secondary: Geometric Mean Titers (GMTs), in Healthy adults 18 to 64 Years of Age

    		 Close Top of page
    End point title
    		 Geometric Mean Titers (GMTs), in Healthy adults 18 to 64 Years of Age [16]
    End point description
    Immunogenicity measured by GMTs after one injection of the investigational influenza virus vaccine, in healthy adults 18 to 64 years of age.
    End point type
    Secondary
    End point timeframe
    21 days after vaccination
    Notes
    [16] - 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: There were no statistical analysis done.
    End point values
    		 Influenza Virus Vaccine (18 to 64 Years) Comparator Influenza Vaccine (18 to 64 Years)
    Number of subjects analysed
    424
    219
    Units: Titers
    geometric mean (confidence interval 95%)
        Strain A/H1N1
    244 (214 to 278)
    512 (426 to 615)
        Strain A/H3N2
    219 (196 to 245)
    485 (415 to 567)
        Strain B
    126 (113 to 140)
    104 (90 to 122)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Unsolicited adverse events were collected from 21 days after the last vaccination (up to day 53) to study termination (up to day 216). All serious adverse events were collected throughout the entire study period (up to day 216).
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    10.0
    Reporting groups
    Reporting group title
    Influenza Virus Vaccine (9 to 17 Years)
    Reporting group description
    		 One injection of the investigational influenza virus vaccine was administered intramuscularly.

    Reporting group title
    Comparator Influenza Vaccine (18 to 64 Years)
    Reporting group description
    		 One injection of the comparator influenza vaccine was administered intramuscularly.

    Reporting group title
    Influenza Virus Vaccine (18 to 64 Years)
    Reporting group description
    		 One injection of the investigational influenza virus vaccine was administered intramuscularly.

    Reporting group title
    Comparator Influenza Vaccine (3 to 8 Years)
    Reporting group description
    		 Two injections of the comparator influenza vaccine were administered intramuscularly.

    Reporting group title
    Influenza Virus Vaccine (3 to 8 Years)
    Reporting group description
    		 Two injections of the investigational influenza virus vaccine were administered intramuscularly.

    Reporting group title
    Comparator Influenza Vaccine (9 to 17 Years)
    Reporting group description
    		 One injection of the comparator influenza vaccine was administered intramuscularly.

    Serious adverse events
    		 Influenza Virus Vaccine (9 to 17 Years) Comparator Influenza Vaccine (18 to 64 Years) Influenza Virus Vaccine (18 to 64 Years) Comparator Influenza Vaccine (3 to 8 Years) Influenza Virus Vaccine (3 to 8 Years) Comparator Influenza Vaccine (9 to 17 Years)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 400 (1.00%)
    2 / 233 (0.86%)
    6 / 460 (1.30%)
    3 / 199 (1.51%)
    3 / 402 (0.75%)
    0 / 199 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    OVARIAN EPITHELIAL CANCER
         subjects affected / exposed
    0 / 400 (0.00%)
    0 / 233 (0.00%)
    1 / 460 (0.22%)
    0 / 199 (0.00%)
    0 / 402 (0.00%)
    0 / 199 (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
    Injury, poisoning and procedural complications
    EYE INJURY
         subjects affected / exposed
    0 / 400 (0.00%)
    0 / 233 (0.00%)
    0 / 460 (0.00%)
    0 / 199 (0.00%)
    1 / 402 (0.25%)
    0 / 199 (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
    Nervous system disorders
    PRESYNCOPE
         subjects affected / exposed
    0 / 400 (0.00%)
    1 / 233 (0.43%)
    0 / 460 (0.00%)
    0 / 199 (0.00%)
    0 / 402 (0.00%)
    0 / 199 (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
    Pregnancy, puerperium and perinatal conditions
    ABORTION SPONTANEOUS
         subjects affected / exposed
    0 / 400 (0.00%)
    0 / 233 (0.00%)
    1 / 460 (0.22%)
    0 / 199 (0.00%)
    0 / 402 (0.00%)
    0 / 199 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 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
    Eye disorders
    VISUAL ACUITY REDUCED TRANSIENTLY
         subjects affected / exposed
    0 / 400 (0.00%)
    0 / 233 (0.00%)
    1 / 460 (0.22%)
    0 / 199 (0.00%)
    0 / 402 (0.00%)
    0 / 199 (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
    Gastrointestinal disorders
    CHRONIC GASTRITIS
         subjects affected / exposed
    0 / 400 (0.00%)
    1 / 233 (0.43%)
    0 / 460 (0.00%)
    0 / 199 (0.00%)
    0 / 402 (0.00%)
    0 / 199 (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
    VOMITING
         subjects affected / exposed
    1 / 400 (0.25%)
    0 / 233 (0.00%)
    0 / 460 (0.00%)
    1 / 199 (0.50%)
    0 / 402 (0.00%)
    0 / 199 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    Respiratory, thoracic and mediastinal disorders
    ASTHMATIC CRISIS
         subjects affected / exposed
    0 / 400 (0.00%)
    0 / 233 (0.00%)
    0 / 460 (0.00%)
    0 / 199 (0.00%)
    1 / 402 (0.25%)
    0 / 199 (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
    Renal and urinary disorders
    RENAL COLIC
         subjects affected / exposed
    1 / 400 (0.25%)
    0 / 233 (0.00%)
    0 / 460 (0.00%)
    0 / 199 (0.00%)
    0 / 402 (0.00%)
    0 / 199 (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
    Infections and infestations
    APPENDICITIS
         subjects affected / exposed
    2 / 400 (0.50%)
    0 / 233 (0.00%)
    1 / 460 (0.22%)
    0 / 199 (0.00%)
    0 / 402 (0.00%)
    0 / 199 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    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
    DIVERTICULITIS
         subjects affected / exposed
    0 / 400 (0.00%)
    0 / 233 (0.00%)
    1 / 460 (0.22%)
    0 / 199 (0.00%)
    0 / 402 (0.00%)
    0 / 199 (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
    DYSENTERY
         subjects affected / exposed
    0 / 400 (0.00%)
    0 / 233 (0.00%)
    1 / 460 (0.22%)
    0 / 199 (0.00%)
    0 / 402 (0.00%)
    0 / 199 (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
    ENCEPHALITIS
         subjects affected / exposed
    0 / 400 (0.00%)
    0 / 233 (0.00%)
    0 / 460 (0.00%)
    1 / 199 (0.50%)
    0 / 402 (0.00%)
    0 / 199 (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
    PNEUMONIA
         subjects affected / exposed
    0 / 400 (0.00%)
    0 / 233 (0.00%)
    0 / 460 (0.00%)
    1 / 199 (0.50%)
    0 / 402 (0.00%)
    0 / 199 (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
    URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 400 (0.00%)
    0 / 233 (0.00%)
    0 / 460 (0.00%)
    0 / 199 (0.00%)
    1 / 402 (0.25%)
    0 / 199 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Influenza Virus Vaccine (9 to 17 Years) Comparator Influenza Vaccine (18 to 64 Years) Influenza Virus Vaccine (18 to 64 Years) Comparator Influenza Vaccine (3 to 8 Years) Influenza Virus Vaccine (3 to 8 Years) Comparator Influenza Vaccine (9 to 17 Years)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    167 / 400 (41.75%)
    128 / 233 (54.94%)
    235 / 460 (51.09%)
    91 / 199 (45.73%)
    153 / 402 (38.06%)
    80 / 199 (40.20%)
    Nervous system disorders
    HEADACHE
         subjects affected / exposed
    52 / 400 (13.00%)
    45 / 233 (19.31%)
    111 / 460 (24.13%)
    26 / 199 (13.07%)
    41 / 402 (10.20%)
    23 / 199 (11.56%)
         occurrences all number
    56
    54
    133
    30
    46
    29
    General disorders and administration site conditions
    CHILLS
         subjects affected / exposed
    18 / 400 (4.50%)
    18 / 233 (7.73%)
    22 / 460 (4.78%)
    12 / 199 (6.03%)
    18 / 402 (4.48%)
    11 / 199 (5.53%)
         occurrences all number
    24
    20
    25
    14
    19
    11
    FATIGUE
         subjects affected / exposed
    25 / 400 (6.25%)
    24 / 233 (10.30%)
    47 / 460 (10.22%)
    12 / 199 (6.03%)
    26 / 402 (6.47%)
    9 / 199 (4.52%)
         occurrences all number
    25
    26
    51
    14
    28
    9
    INJECTION SITE ERYTHEMA
         subjects affected / exposed
    7 / 400 (1.75%)
    12 / 233 (5.15%)
    27 / 460 (5.87%)
    7 / 199 (3.52%)
    12 / 402 (2.99%)
    3 / 199 (1.51%)
         occurrences all number
    7
    12
    27
    8
    12
    3
    INJECTION SITE HAEMORRHAGE
         subjects affected / exposed
    9 / 400 (2.25%)
    15 / 233 (6.44%)
    25 / 460 (5.43%)
    13 / 199 (6.53%)
    26 / 402 (6.47%)
    1 / 199 (0.50%)
         occurrences all number
    9
    15
    25
    14
    28
    1
    INJECTION SITE INDURATION
         subjects affected / exposed
    28 / 400 (7.00%)
    24 / 233 (10.30%)
    38 / 460 (8.26%)
    16 / 199 (8.04%)
    23 / 402 (5.72%)
    13 / 199 (6.53%)
         occurrences all number
    28
    24
    38
    18
    24
    13
    INJECTION SITE PAIN
         subjects affected / exposed
    117 / 400 (29.25%)
    70 / 233 (30.04%)
    117 / 460 (25.43%)
    59 / 199 (29.65%)
    97 / 402 (24.13%)
    58 / 199 (29.15%)
         occurrences all number
    120
    70
    121
    75
    129
    58
    INJECTION SITE SWELLING
         subjects affected / exposed
    28 / 400 (7.00%)
    15 / 233 (6.44%)
    29 / 460 (6.30%)
    20 / 199 (10.05%)
    34 / 402 (8.46%)
    14 / 199 (7.04%)
         occurrences all number
    28
    15
    29
    24
    37
    14
    MALAISE
         subjects affected / exposed
    18 / 400 (4.50%)
    28 / 233 (12.02%)
    56 / 460 (12.17%)
    19 / 199 (9.55%)
    37 / 402 (9.20%)
    8 / 199 (4.02%)
         occurrences all number
    18
    29
    61
    19
    41
    8
    Skin and subcutaneous tissue disorders
    HYPERHIDROSIS
         subjects affected / exposed
    4 / 400 (1.00%)
    11 / 233 (4.72%)
    24 / 460 (5.22%)
    4 / 199 (2.01%)
    8 / 402 (1.99%)
    3 / 199 (1.51%)
         occurrences all number
    4
    14
    26
    4
    8
    3
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    11 / 400 (2.75%)
    15 / 233 (6.44%)
    32 / 460 (6.96%)
    3 / 199 (1.51%)
    10 / 402 (2.49%)
    5 / 199 (2.51%)
         occurrences all number
    11
    16
    38
    3
    12
    5
    MYALAGIA
         subjects affected / exposed
    35 / 400 (8.75%)
    38 / 233 (16.31%)
    66 / 460 (14.35%)
    17 / 199 (8.54%)
    34 / 402 (8.46%)
    25 / 199 (12.56%)
         occurrences all number
    36
    39
    74
    19
    41
    26

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Feb 2007
    To include children / adolescents aged 9 to 17 and adults aged 18 to 64 years to the originally proposed study population.
    26 Jun 2007
    The primary immunogenicity objective, which previously included all 3 age strata and was amended to refer to the adults aged 18 to 64 only. The secondary objective was also amended to refer to adults aged 18 to 64 years for one injection of Fluvirin, children/adolescents aged 9 to 17 years for one injection of either Agrippal or Fluvirin and children aged 3 to 8 years for two injections of either Agrippal or Fluvirin.

    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.
    NA

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/22691101
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri Apr 26 08:43:53 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA