A Clinical Trial of CSL's 2009 H1N1 Influenza Vaccine (CSL425) in Healthy Children

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CSL Limited
ClinicalTrials.gov Identifier:
NCT00940108
First received: July 13, 2009
Last updated: October 28, 2013
Last verified: October 2013
Results First Received: July 9, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition: Influenza Caused by the Novel Influenza A (H1N1) Virus
Intervention: Biological: CSL425

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
One randomized participant withdrew consent prior to vaccine administration and was not included in the participant flow data or in any analysis population.

Reporting Groups
  Description
CSL425 (15 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (15 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.

Participant Flow:   Overall Study
    CSL425 (15 Mcg) Cohort A     CSL425 (30 Mcg) Cohort A     CSL425 (15 Mcg) Cohort B     CSL425 (30 Mcg) Cohort B  
STARTED     82     80     103     104  
COMPLETED     77     71     100     99  
NOT COMPLETED     5     9     3     5  
Adverse Event                 2                 4                 0                 2  
Withdrew Consent                 2                 1                 0                 1  
Dose 2 contraindicated                 1                 1                 0                 1  
Declined further vaccination                 0                 1                 3                 0  
Refused - pyrexia after Dose 1                 0                 1                 0                 0  
Viral illness after Dose 1                 0                 1                 0                 0  
Diagnosed with H1N1                 0                 0                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
CSL425 (15 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (15 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
Total Total of all reporting groups

Baseline Measures
    CSL425 (15 Mcg) Cohort A     CSL425 (30 Mcg) Cohort A     CSL425 (15 Mcg) Cohort B     CSL425 (30 Mcg) Cohort B     Total  
Number of Participants  
[units: participants]
  82     80     103     104     369  
Age  
[units: years]
Mean ± Standard Deviation
  1.68  ± 0.67     1.73  ± 0.74     5.78  ± 1.69     5.66  ± 1.74     3.96  ± 2.42  
Gender  
[units: participants]
         
Female     41     41     53     49     184  
Male     41     39     50     55     185  



  Outcome Measures
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1.  Primary:   Haemagglutination Inhibition (HI) Antibody Titre Seroconversion Rate After the First Vaccination   [ Time Frame: Before and 21 days after the first vaccination ]

Measure Type Primary
Measure Title Haemagglutination Inhibition (HI) Antibody Titre Seroconversion Rate After the First Vaccination
Measure Description HI antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination HI antibody titre of 1:40 or more; or participants with a pre-vaccination HI titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre.
Time Frame Before and 21 days after the first vaccination  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Evaluable Population (for the first vaccination) comprised all randomised participants who received the first study vaccination; provided both pre- and post-vaccination blood samples; were not excluded from analyses (eg, for the use of a prohibited medication or a laboratory-confirmed 2009 H1N1 infection between Visit 1 and Visit 3).

Reporting Groups
  Description
CSL425 (15 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (15 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.

Measured Values
    CSL425 (15 Mcg) Cohort A     CSL425 (30 Mcg) Cohort A     CSL425 (15 Mcg) Cohort B     CSL425 (30 Mcg) Cohort B  
Number of Participants Analyzed  
[units: participants]
  76     73     98     99  
Haemagglutination Inhibition (HI) Antibody Titre Seroconversion Rate After the First Vaccination  
[units: percentage of participants]
Number ( 95% Confidence Interval )
  88.2  
  ( 78.7 to 94.4 )  
  97.3  
  ( 90.5 to 99.7 )  
  85.7  
  ( 77.2 to 92.0 )  
  91.9  
  ( 84.7 to 96.4 )  

No statistical analysis provided for Haemagglutination Inhibition (HI) Antibody Titre Seroconversion Rate After the First Vaccination



2.  Primary:   HI Antibody Titre Seroconversion Rate After the Second Vaccination   [ Time Frame: Before and 21 days after the second vaccination ]

Measure Type Primary
Measure Title HI Antibody Titre Seroconversion Rate After the Second Vaccination
Measure Description HI antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination HI antibody titre of 1:40 or more; or participants with a pre-vaccination HI titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre.
Time Frame Before and 21 days after the second vaccination  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Evaluable Population (for the second vaccination) comprised all randomised participants who received the second study vaccination; provided both pre- and post-vaccination blood samples; were not excluded from analyses (eg, for the use of a prohibited medication or a laboratory-confirmed 2009 H1N1 infection between Visit 1 and Visit 3).

Reporting Groups
  Description
CSL425 (15 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (15 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.

Measured Values
    CSL425 (15 Mcg) Cohort A     CSL425 (30 Mcg) Cohort A     CSL425 (15 Mcg) Cohort B     CSL425 (30 Mcg) Cohort B  
Number of Participants Analyzed  
[units: participants]
  64     69     95     96  
HI Antibody Titre Seroconversion Rate After the Second Vaccination  
[units: percentage of participants]
Number ( 95% Confidence Interval )
  96.9  
  ( 89.2 to 99.6 )  
  98.6  
  ( 92.2 to 100.0 )  
  97.9  
  ( 92.6 to 99.7 )  
  96.9  
  ( 91.1 to 99.4 )  

No statistical analysis provided for HI Antibody Titre Seroconversion Rate After the Second Vaccination



3.  Primary:   Geometric Mean Fold Increase (GMFI) in the HI Antibody Titre After the First Vaccination   [ Time Frame: Before and 21 days after the first vaccination ]

Measure Type Primary
Measure Title Geometric Mean Fold Increase (GMFI) in the HI Antibody Titre After the First Vaccination
Measure Description GMFI in HI antibody titre was defined as the geometric mean of the fold increase in the post-vaccination antibody titre over the pre-vaccination antibody titre.
Time Frame Before and 21 days after the first vaccination  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Evaluable Population (for the first vaccination) comprised all randomised participants who received the first study vaccination; provided both pre- and post-vaccination blood samples; were not excluded from analyses (eg, for the use of a prohibited medication or a laboratory-confirmed 2009 H1N1 infection between Visit 1 and Visit 3).

Reporting Groups
  Description
CSL425 (15 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (15 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.

Measured Values
    CSL425 (15 Mcg) Cohort A     CSL425 (30 Mcg) Cohort A     CSL425 (15 Mcg) Cohort B     CSL425 (30 Mcg) Cohort B  
Number of Participants Analyzed  
[units: participants]
  76     73     98     99  
Geometric Mean Fold Increase (GMFI) in the HI Antibody Titre After the First Vaccination  
[units: geometric mean fold increase]
Geometric Mean ( 95% Confidence Interval )
  13.95  
  ( 11.39 to 17.09 )  
  22.17  
  ( 17.87 to 27.49 )  
  13.25  
  ( 10.84 to 16.19 )  
  15.93  
  ( 12.87 to 19.71 )  

No statistical analysis provided for Geometric Mean Fold Increase (GMFI) in the HI Antibody Titre After the First Vaccination



4.  Primary:   GMFI in the HI Antibody Titre After the Second Vaccination   [ Time Frame: Before and 21 days after the second vaccination ]

Measure Type Primary
Measure Title GMFI in the HI Antibody Titre After the Second Vaccination
Measure Description GMFI in HI antibody titre was defined as the geometric mean of the fold increase in the post-vaccination antibody titre over the pre-vaccination antibody titre.
Time Frame Before and 21 days after the second vaccination  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Evaluable Population (for the second vaccination) comprised all randomised participants who received the second study vaccination; provided both pre- and post-vaccination blood samples; were not excluded from analyses (eg, for the use of a prohibited medication or a laboratory-confirmed 2009 H1N1 infection between Visit 1 and Visit 3).

Reporting Groups
  Description
CSL425 (15 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (15 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.

Measured Values
    CSL425 (15 Mcg) Cohort A     CSL425 (30 Mcg) Cohort A     CSL425 (15 Mcg) Cohort B     CSL425 (30 Mcg) Cohort B  
Number of Participants Analyzed  
[units: participants]
  64     69     95     96  
GMFI in the HI Antibody Titre After the Second Vaccination  
[units: geometric mean fold increase]
Geometric Mean ( 95% Confidence Interval )
  57.64  
  ( 42.87 to 77.50 )  
  72.93  
  ( 56.10 to 94.80 )  
  37.48  
  ( 28.33 to 49.58 )  
  37.06  
  ( 28.77 to 47.75 )  

No statistical analysis provided for GMFI in the HI Antibody Titre After the Second Vaccination



5.  Primary:   Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More After the First Vaccination   [ Time Frame: 21 days after the first vaccination ]

Measure Type Primary
Measure Title Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More After the First Vaccination
Measure Description No text entered.
Time Frame 21 days after the first vaccination  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Evaluable Population (for the first vaccination) comprised all randomised participants who received the first study vaccination; provided both pre- and post-vaccination blood samples; were not excluded from analyses (eg, for the use of a prohibited medication or a laboratory-confirmed 2009 H1N1 infection between Visit 1 and Visit 3).

Reporting Groups
  Description
CSL425 (15 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (15 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.

Measured Values
    CSL425 (15 Mcg) Cohort A     CSL425 (30 Mcg) Cohort A     CSL425 (15 Mcg) Cohort B     CSL425 (30 Mcg) Cohort B  
Number of Participants Analyzed  
[units: participants]
  76     73     98     99  
Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More After the First Vaccination  
[units: percentage of participants]
Number ( 95% Confidence Interval )
  92.1  
  ( 83.6 to 97.0 )  
  100.0  
  ( 95.1 to 100.0 )  
  92.9  
  ( 85.8 to 97.1 )  
  96.0  
  ( 90.0 to 98.9 )  

No statistical analysis provided for Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More After the First Vaccination



6.  Primary:   Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More After the Second Vaccination   [ Time Frame: 21 days after the second vaccination ]

Measure Type Primary
Measure Title Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More After the Second Vaccination
Measure Description No text entered.
Time Frame 21 days after the second vaccination  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Evaluable Population (for the second vaccination) comprised all randomised participants who received the second study vaccination; provided both pre- and post-vaccination blood samples; were not excluded from analyses (eg, for the use of a prohibited medication or a laboratory-confirmed 2009 H1N1 infection between Visit 1 and Visit 3).

Reporting Groups
  Description
CSL425 (15 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (15 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.

Measured Values
    CSL425 (15 Mcg) Cohort A     CSL425 (30 Mcg) Cohort A     CSL425 (15 Mcg) Cohort B     CSL425 (30 Mcg) Cohort B  
Number of Participants Analyzed  
[units: participants]
  64     69     95     96  
Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More After the Second Vaccination  
[units: percentage of participants]
Number ( 95% Confidence Interval )
  100.0  
  ( 94.4 to 100.0 )  
  100.0  
  ( 94.8 to 100.0 )  
  100.0  
  ( 96.2 to 100.0 )  
  100.0  
  ( 96.2 to 100.0 )  

No statistical analysis provided for Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More After the Second Vaccination



7.  Secondary:   Frequency and Intensity of Solicited Adverse Events (AEs) After the First or Second Vaccination   [ Time Frame: During the 7 days after each vaccination ]

Measure Type Secondary
Measure Title Frequency and Intensity of Solicited Adverse Events (AEs) After the First or Second Vaccination
Measure Description Solicited AEs included AEs that were specifically sought for. Grade 3 solicited AE definitions: Cried when limb was moved/spontaneously painful (Cohort A) or prevented normal daily activities (Cohort B) for injection site pain; Size > 100 mm for injection site redness and induration/swelling; Temperature > 103.1°F (39.5°C) for fevers; Prevented normal daily activities or required medical intervention for all other systemic AEs.
Time Frame During the 7 days after each vaccination  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Reporting Groups
  Description
CSL425 (15 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (15 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.

Measured Values
    CSL425 (15 Mcg) Cohort A     CSL425 (30 Mcg) Cohort A     CSL425 (15 Mcg) Cohort B     CSL425 (30 Mcg) Cohort B  
Number of Participants Analyzed  
[units: participants]
  82     80     103     104  
Frequency and Intensity of Solicited Adverse Events (AEs) After the First or Second Vaccination  
[units: percentage of participants]
       
Any solicited local AE     69.5     63.8     68.0     71.2  
Any pain at injection site     48.8     43.8     59.2     64.4  
Grade 3 pain at injection site     1.2     1.3     0     1.0  
Any redness at injection site     53.7     38.8     37.9     37.5  
Grade 3 redness at injection site     0     1.3     2.9     2.9  
Any swelling/induration at injection site     30.5     32.5     25.2     26.9  
Grade 3 swelling/induration at injection site     0     2.5     0     4.8  
Any solicited systemic AE     79.3     93.8     54.4     61.5  
Any nausea/vomiting     13.4     30.0     15.5     20.2  
Grade 3 nausea/vomiting     1.2     1.3     0     1.0  
Any diarrhoea     26.8     32.5     12.6     12.5  
Grade 3 diarrhoea     1.2     0     0     0  
Any loss of appetite     40.2     50.0     NA [1]   NA [1]
Grade 3 loss of appetite     1.2     0     NA [1]   NA [1]
Any irritability     63.4     72.5     NA [1]   NA [1]
Grade 3 irritability     2.4     1.3     NA [1]   NA [1]
Any fever     50.0     71.3     20.4     29.8  
Grade 3 fever     1.2     8.8     0     2.9  
Any headache     NA [2]   NA [2]   27.2     23.1  
Grade 3 headache     NA [2]   NA [2]   0     1  
Any muscle ache     NA [2]   NA [2]   15.5     22.1  
Grade 3 muscle ache     NA [2]   NA [2]   0     1  
Any malaise     NA [2]   NA [2]   19.4     26.9  
Grade 3 malaise     NA [2]   NA [2]   0     1.9  
[1] Not solicited for in Cohort B
[2] Not solicited for in Cohort A

No statistical analysis provided for Frequency and Intensity of Solicited Adverse Events (AEs) After the First or Second Vaccination



8.  Secondary:   Duration of Solicited AEs After the First Vaccination   [ Time Frame: During the 7 days after the first vaccination and up to Day 20 after the first vaccination if AE is ongoing at Day 7. ]

Measure Type Secondary
Measure Title Duration of Solicited AEs After the First Vaccination
Measure Description Solicited AEs included AEs that were specifically sought for.
Time Frame During the 7 days after the first vaccination and up to Day 20 after the first vaccination if AE is ongoing at Day 7.  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Reporting Groups
  Description
CSL425 (15 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (15 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.

Measured Values
    CSL425 (15 Mcg) Cohort A     CSL425 (30 Mcg) Cohort A     CSL425 (15 Mcg) Cohort B     CSL425 (30 Mcg) Cohort B  
Number of Participants Analyzed  
[units: participants]
  82     80     103     104  
Duration of Solicited AEs After the First Vaccination  
[units: days]
Mean ± Standard Deviation
       
Pain at injection site     1.48  ± 0.677     1.52  ± 0.823     1.91  ± 1.221     1.80  ± 1.016  
Redness at injection site     2.08  ± 1.382     2.23  ± 1.602     2.26  ± 1.347     2.00  ± 1.134  
Swelling/induration at injection site     1.88  ± 0.957     1.64  ± 0.745     1.60  ± 0.737     2.04  ± 1.136  
Nausea/vomiting     1.33  ± 0.500     1.05  ± 0.213     1.18  ± 0.405     1.53  ± 1.837  
Diarrhoea     1.67  ± 1.328     1.55  ± 0.945     1.11  ± 0.333     1.17  ± 0.577  
Loss of appetite     2.32  ± 1.906     1.97  ± 1.447     NA  ± NA [1]   NA  ± NA [1]
Irritability     1.78  ± 1.560     1.73  ± 1.574     NA  ± NA [1]   NA  ± NA [1]
Fever     1.77  ± 1.547     1.52  ± 1.079     1.40  ± 0.737     1.54  ± 1.319  
Headache     NA  ± NA [2]   NA  ± NA [2]   2.04  ± 2.911     1.63  ± 1.149  
Muscle ache     NA  ± NA [2]   NA  ± NA [2]   1.45  ± 0.688     1.86  ± 2.175  
Malaise     NA  ± NA [2]   NA  ± NA [2]   1.60  ± 0.910     1.69  ± 1.966  
[1] Not solicited for in Cohort B
[2] Not solicited for in Cohort A

No statistical analysis provided for Duration of Solicited AEs After the First Vaccination



9.  Secondary:   Duration of Solicited AEs After the Second Vaccination   [ Time Frame: During the 7 days after the second vaccination and up to Day 20 after the second vaccination if AE was ongoing at Day 7. ]

Measure Type Secondary
Measure Title Duration of Solicited AEs After the Second Vaccination
Measure Description Solicited AEs included AEs that were specifically sought for.
Time Frame During the 7 days after the second vaccination and up to Day 20 after the second vaccination if AE was ongoing at Day 7.  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Reporting Groups
  Description
CSL425 (15 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (15 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.

Measured Values
    CSL425 (15 Mcg) Cohort A     CSL425 (30 Mcg) Cohort A     CSL425 (15 Mcg) Cohort B     CSL425 (30 Mcg) Cohort B  
Number of Participants Analyzed  
[units: participants]
  77     71     100     99  
Duration of Solicited AEs After the Second Vaccination  
[units: days]
Mean ± Standard Deviation
       
Pain at injection site     1.67  ± 0.966     1.64  ± 1.002     1.90  ± 1.179     1.80  ± 1.040  
Redness at injection site     1.69  ± 1.004     2.14  ± 1.037     1.92  ± 1.055     1.70  ± 0.822  
Swelling/induration at injection site     1.74  ± 0.872     2.32  ± 1.108     2.24  ± 1.348     2.27  ± 1.751  
Nausea/vomiting     5.00  ± 8.832     1.00  ± 0.000     1.43  ± 0.787     1.11  ± 0.333  
Diarrhoea     3.40  ± 3.777     1.25  ± 0.452     1.40  ± 0.894     2.00  ± 1.000  
Loss of appetite     3.15  ± 4.475     1.73  ± 0.883     NA  ± NA [1]   NA  ± NA [1]
Irritability     2.57  ± 2.410     2.10  ± 1.533     NA  ± NA [1]   NA  ± NA [1]
Fever     2.14  ± 3.005     1.63  ± 1.165     1.54  ± 0.877     1.67  ± 1.414  
Headache     NA  ± NA [2]   NA  ± NA [2]   1.33  ± 0.686     1.73  ± 2.412  
Muscle ache     NA  ± NA [2]   NA  ± NA [2]   1.60  ± 0.516     1.29  ± 0.756  
Malaise     NA  ± NA [2]   NA  ± NA [2]   1.20  ± 0.422     2.00  ± 1.826  
[1] Not solicited for in Cohort B
[2] Not solicited for in Cohort A

No statistical analysis provided for Duration of Solicited AEs After the Second Vaccination



10.  Secondary:   Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)   [ Time Frame: Up to 180 days after the last vaccination ]

Measure Type Secondary
Measure Title Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)
Measure Description An AESI was defined as an AE for which the association with seasonal influenza vaccine was unclear. A NOCI was defined as the diagnosis of a new medical condition that was chronic in nature, including those potentially controllable by medication (eg, diabetes, asthma).
Time Frame Up to 180 days after the last vaccination  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Reporting Groups
  Description
CSL425 (15 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (15 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.

Measured Values
    CSL425 (15 Mcg) Cohort A     CSL425 (30 Mcg) Cohort A     CSL425 (15 Mcg) Cohort B     CSL425 (30 Mcg) Cohort B  
Number of Participants Analyzed  
[units: participants]
  82     80     103     104  
Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)  
[units: percentage of participants]
       
At least one SAE     4.9     1.3     1.0     1.0  
Related SAE     0     0     0     1  
At least one AESI     2.4     1.3     0     0  
Related AESI     0     0     0     0  
At least one NOCI     1.2     3.8     1.9     0  
Related NOCI     0     0     0     0  

No statistical analysis provided for Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)



11.  Secondary:   Frequency and Intensity of Unsolicited Adverse Events After the First or Second Vaccination   [ Time Frame: During the 21 days after each vaccination; up to 180 days after the last vaccination for SAEs, AESIs, and NOCIs ]

Measure Type Secondary
Measure Title Frequency and Intensity of Unsolicited Adverse Events After the First or Second Vaccination
Measure Description Unsolicited AEs included AEs other than those specifically sought for. Grade 1 unsolicited AE definition: Easily tolerated and did not interfere with normal daily activities. Grade 2 unsolicited AE definition: Some interference with normal daily activities. Grade 3 unsolicited AE definition: Prevented normal daily activities.
Time Frame During the 21 days after each vaccination; up to 180 days after the last vaccination for SAEs, AESIs, and NOCIs  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Reporting Groups
  Description
CSL425 (15 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort A Participants aged 6 months to less than 3 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (15 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (15 mcg of haemagglutinin antigen per 0.25 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.
CSL425 (30 Mcg) Cohort B Participants aged 3 years to less than 9 years received two doses of CSL425 (30 mcg of haemagglutinin antigen per 0.5 mL dose) by intramuscular injection into the deltoid region of the arm on Day 0 and Day 21.

Measured Values
    CSL425 (15 Mcg) Cohort A     CSL425 (30 Mcg) Cohort A     CSL425 (15 Mcg) Cohort B     CSL425 (30 Mcg) Cohort B  
Number of Participants Analyzed  
[units: participants]
  82     80     103     104  
Frequency and Intensity of Unsolicited Adverse Events After the First or Second Vaccination  
[units: percentage of participants]
       
At least one unsolicited AE     78.0     82.5     67.0     76.0  
Grade 1 unsolicited AE     26.8     33.8     27.2     37.5  
Grade 2 unsolicited AE     41.5     41.3     37.9     26.9  
Grade 3 unsolicited AE     9.8     7.5     1.9     11.5  

No statistical analysis provided for Frequency and Intensity of Unsolicited Adverse Events After the First or Second Vaccination




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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