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

• Sponsor: Seqirus (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00938639
• Collaborator: (none)
• Enrollment: 240
• Location: 1
• Arms: 2
• Duration (Months): 8
• Patients Per Site Per Month: 30.1

Study Details

Study Description

Brief Summary

The purpose of the study is to determine whether CSL425 is a safe and effective vaccine for eliciting an immune response to H1N1 influenza in healthy adults.

Condition or Disease	Intervention/Treatment	Phase
Influenza Caused by the Novel Influenza A (H1N1) Virus	Biological: CSL425; Biological: CSL425	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase II, Single-centre, Randomised, Observer-blind Study to Evaluate the Immunogenicity, Safety and Tolerability of CSL's Monovalent H1N1 Influenza Virus Vaccine in Healthy Adults Aged 18 to < 65 Years.
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CSL425 (15 mcg) 15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	Biological: CSL425; CSL's 2009 H1N1 Influenza Vaccine, thimerosal 0.01% (weight/volume)
Experimental: CSL425 (30 mcg) 30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	Biological: CSL425; CSL's 2009 H1N1 Influenza Vaccine, thimerosal 0.01% (weight/volume)

Outcome Measures

Primary Outcome Measures

1. Haemagglutination Inhibition (HI) and Microneutralisation (MN) Antibody Titre Seroconversion Rate After the First Vaccination [Before and 21 days after the first vaccination]

   Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination antibody titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre.

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

   Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination antibody titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre.

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

   GMFI in antibody titre was defined as the geometric mean of the fold increase in the post-vaccination antibody titre over the pre-vaccination antibody titre.

4. GMFI in the HI and MN Antibody Titer After the Second Vaccination [Before and 21 days after the second vaccination]

   GMFI in antibody titre was defined as the geometric mean of the fold increase in the post-vaccination antibody titre over the pre-vaccination antibody titre.

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

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

Secondary Outcome Measures

1. HI and MN Antibody Titre Seroconversion Rate After the First Vaccination by Age Group [Before and 21 days after the first vaccination]

   Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination antibody titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre. Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.

2. HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination by Age Group [Before and 21 days after the second vaccination]

   Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination antibody titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre. Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.

3. GMFI in the HI and MN Antibody Titre After the First Vaccination by Age Group [Before and 21 days after the first vaccination]

   GMFI in antibody titre was defined as the geometric mean of the fold increase in the post-vaccination antibody titre over the pre-vaccination antibody titre. Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.

4. GMFI in the HI and MN Antibody Titre After the Second Vaccination by Age Group [Before and 21 days after the second vaccination]

   GMFI in antibody titre was defined as the geometric mean of the fold increase in the post-vaccination antibody titre over the pre-vaccination antibody titre. Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.

5. Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination by Age Group [21 days after the first vaccination]

   Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.

6. Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination by Age Group [21 days after the second vaccination]

   Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.

7. Percentage of Participants With a Baseline Titre Less Than 1:10 Achieving Seroconversion After Vaccination [Before and 21 days after each vaccination]

   The number of participants with a baseline titre less than 1:10 differed according to antibody assay (HI or MN) and is shown in the category titles accordingly. The total number of participants analysed includes all evaluable participants; however, the analysis is stratified by baseline titre and those participants with a baseline titre less than 1:10 are presented in this outcome measure while those with a baseline titre of 1:10 or more are presented in a separate outcome measure. Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre.

8. Percentage of Participants With a Baseline Titre Greater Than or Equal to 1:10 Achieving Seroconversion After Vaccination [Before and 21 days after each vaccination]

   The number of participants with a baseline titre greater than or equal to 1:10 differed according to antibody assay (HI or MN) and is shown in the category titles accordingly. The total number of participants analysed includes all evaluable participants; however, the analysis is stratified by baseline titre and those participants with a baseline titre of 1:10 or more are presented in this outcome measure while those with a baseline titre less than 1:10 are presented in a separate outcome measure. Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre (ie, a significant increase in antibody titre after vaccination).

9. GMFI in the HI Antibody Titre 180 Days After the Second Vaccination [21 days and 180 days after the second vaccination]

   The GMFI in antibody titre was calculated by taking the anti-logs of the means of the log transformed fold-increases in the antibody titre 180 days after the second vaccination over the antibody titre 21 days after the second vaccination.

10. Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More 180 Days After the Second Vaccination [180 days after the second vaccination]

11. Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination [From Day 0 to Day 6 after the first vaccination]

    Solicited AEs included AEs that were specifically sought for. Grade 3 solicited AE definitions: Prevented normal daily activities; Size > 100 mm for injection site redness, induration/swelling, and bruising.

12. Duration of Solicited Local AEs After the First Vaccination [From Day 0 to Day 6 after the first vaccination and up to Day 20 after the first vaccination if AE is ongoing at Day 7]

    Solicited AEs included AEs that were specifically sought for.

13. Frequency and Intensity of Solicited Local AEs After the Second Vaccination [From Day 0 to Day 6 after the second vaccination]

    Solicited AEs included AEs that were specifically sought for. Grade 3 solicited AE definitions: Prevented normal daily activities; Size > 100 mm for injection site redness, induration/swelling, and bruising.

14. Duration of Solicited Local AEs After the Second Vaccination [From Day 0 to Day 6 after the second vaccination and up to Day 20 after the second vaccination if AE is ongoing at Day 7]

    Solicited AEs included AEs that were specifically sought for.

15. Frequency and Intensity of Solicited Systemic AEs After the First Vaccination [From Day 0 to Day 6 after the first vaccination]

    Solicited AEs included AEs that were specifically sought for. Grade 3 solicited AE definitions: Prevented normal daily activities; Temperature 102.2°F (39.0°C) or more for fevers.

16. Duration of Solicited Systemic AEs After the First Vaccination [From Day 0 to Day 6 after the first vaccination and up to Day 20 after the first vaccination if AE is ongoing at Day 7]

    Solicited AEs included AEs that were specifically sought for.

17. Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination [From Day 0 to Day 6 after the second vaccination]

    Solicited AEs included AEs that were specifically sought for. Grade 3 solicited AE definitions: Prevented normal daily activities; Temperature 102.2°F (39.0°C) or more for fevers.

18. Duration of Solicited Systemic AEs After the Second Vaccination [From Day 0 to Day 6 after the second vaccination and up to Day 20 after the second vaccination if AE is ongoing at Day 7]

    Solicited AEs included AEs that were specifically sought for.

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

    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).

20. Frequency and Intensity of Unsolicited AEs [From Day 0 to Day 20 after vaccination; up to 180 days after the last vaccination for SAEs, AESIs, and NOCIs]

    Unsolicited AEs included AEs other than those specifically sought for. The grading definitions were: Mild (Grade 1): Symptoms were easily tolerated and did not interfere with daily activities. Moderate (Grade 2): Enough discomfort to cause some interference with daily activities. Severe (Grade 3): Incapacitating, with inability to work or do usual activities.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female aged >= 18 to < 65 years at the time of providing informed consent.

Exclusion Criteria:

• Known hypersensitivity to a previous dose of influenza virus vaccine or allergy to eggs, chicken protein, thiomersal, neomycin, polymyxin, or any components of the Study Vaccine.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Study Site	Adelaide	South Australia	Australia	5000

Sponsors and Collaborators

• Seqirus

Investigators

• Study Director: Director, Vaccines Clinical Development, Seqirus

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Seqirus
• ClinicalTrials.gov Identifier: NCT00938639
• Other Study ID Numbers: CSLCT-CAL-09-59
• First Posted: Jul 14, 2009
• Last Update Posted: Jun 28, 2018
• Last Verified: Apr 1, 2018

• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Period Title: Overall Study
STARTED	120	120
COMPLETED	117	116
NOT COMPLETED	3	4

Baseline Characteristics

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)	Total
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	Total of all reporting groups
Overall Participants	120	120	240
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.6 (15.12)	42.9 (15.39)	43.7 (15.25)
Sex: Female, Male (Count of Participants)
Female	67 55.8%	67 55.8%	134 55.8%
Male	53 44.2%	53 44.2%	106 44.2%

Outcome Measures

1. Primary Outcome

Title	Haemagglutination Inhibition (HI) and Microneutralisation (MN) Antibody Titre Seroconversion Rate After the First Vaccination
Description	Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination antibody titre of 1:40 or more; or participants with a pre-vaccination 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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	120	119
Seroconversion rate - HI	74.2 61.8%	81.5 67.9%
Seroconversion rate - MN	77.5 64.6%	75.6 63%

2. Primary Outcome

Title	HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination
Description	Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination antibody titre of 1:40 or more; or participants with a pre-vaccination 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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	117	115
Seroconversion rate - HI	82.1 68.4%	89.6 74.7%
Seroconversion rate - MN	87.2 72.7%	83.5 69.6%

3. Primary Outcome

Title	Geometric Mean Fold Increase (GMFI) in the HI and MN Antibody Titre After the First Vaccination
Description	GMFI in 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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	120	119
GMFI - HI	11.83	19.54
GMFI - MN	24.83	39.70

4. Primary Outcome

Title	GMFI in the HI and MN Antibody Titer After the Second Vaccination
Description	GMFI in 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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	117	115
GMFI - HI	16.00	23.30
GMFI - MN	32.30	46.50

5. Primary Outcome

Title	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination
Time Frame	21 days after the first vaccination

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	120	119
Participants with HI titer ≥ 1:40	95.0 79.2%	89.1 74.3%
Participants with MN titer ≥ 1:40	88.3 73.6%	83.2 69.3%

6. Primary Outcome

Title	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination
Time Frame	21 days after the second vaccination

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	117	115
Participants with HI titer ≥ 1:40	98.3 81.9%	96.5 80.4%
Participants with MN titer ≥ 1:40	95.7 79.8%	92.2 76.8%

7. Secondary Outcome

Title	HI and MN Antibody Titre Seroconversion Rate After the First Vaccination by Age Group
Description	Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination antibody titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre. Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.
Time Frame	Before and 21 days after the first vaccination

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	CSL425 (15 mcg), Adult	CSL425 (15 mcg), Older Adult	CSL425 (30 mcg), Adult	CSL425 (30 mcg), Older Adult
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	58	62	61	58
Seroconversion rate - HI	77.6 64.7%	71.0 59.2%	85.2 35.5%	77.6 NaN
Seroconversion rate - MN	82.8 69%	72.6 60.5%	83.6 34.8%	67.2 NaN

8. Secondary Outcome

Title	HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination by Age Group
Description	Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination antibody titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre. Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.
Time Frame	Before and 21 days after the second vaccination

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	CSL425 (15 mcg), Adult	CSL425 (15 mcg), Older Adult	CSL425 (30 mcg), Adult	CSL425 (30 mcg), Older Adult
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	55	62	58	57
Seroconversion rate - HI	83.6 69.7%	80.6 67.2%	87.9 36.6%	91.2 NaN
Seroconversion rate - MN	89.1 74.3%	85.5 71.3%	86.2 35.9%	80.7 NaN

9. Secondary Outcome

Title	GMFI in the HI and MN Antibody Titre After the First Vaccination by Age Group
Description	GMFI in antibody titre was defined as the geometric mean of the fold increase in the post-vaccination antibody titre over the pre-vaccination antibody titre. Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.
Time Frame	Before and 21 days after the first vaccination

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	CSL425 (15 mcg), Adult	CSL425 (15 mcg), Older Adult	CSL425 (30 mcg), Adult	CSL425 (30 mcg), Older Adult
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	58	62	61	58
GMFI - HI	15.13	9.39	25.79	14.60
GMFI - MN	36.73	17.21	54.91	28.22

10. Secondary Outcome

Title	GMFI in the HI and MN Antibody Titre After the Second Vaccination by Age Group
Description	GMFI in antibody titre was defined as the geometric mean of the fold increase in the post-vaccination antibody titre over the pre-vaccination antibody titre. Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.
Time Frame	Before and 21 days after the second vaccination

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	CSL425 (15 mcg), Adult	CSL425 (15 mcg), Older Adult	CSL425 (30 mcg), Adult	CSL425 (30 mcg), Older Adult
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	55	62	58	57
GMFI - HI	18.00	14.41	26.01	20.82
GMFI - MN	37.95	28.00	55.79	38.63

11. Secondary Outcome

Title	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination by Age Group
Description	Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.
Time Frame	21 days after the first vaccination

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	CSL425 (15 mcg), Adult	CSL425 (15 mcg), Older Adult	CSL425 (30 mcg), Adult	CSL425 (30 mcg), Older Adult
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	58	62	61	58
Participants with HI titer ≥ 1:40	96.6 80.5%	93.5 77.9%	98.4 41%	79.3 NaN
Participants with MN titer ≥ 1:40	94.8 79%	82.3 68.6%	95.1 39.6%	70.7 NaN

12. Secondary Outcome

Title	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination by Age Group
Description	Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.
Time Frame	21 days after the second vaccination

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	CSL425 (15 mcg), Adult	CSL425 (15 mcg), Older Adult	CSL425 (30 mcg), Adult	CSL425 (30 mcg), Older Adult
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	55	62	58	57
Participants with HI titer ≥ 1:40	98.2 81.8%	98.4 82%	100.0 41.7%	93.0 NaN
Participants with MN titer ≥ 1:40	100.0 83.3%	91.9 76.6%	100.0 41.7%	84.2 NaN

13. Secondary Outcome

Title	Percentage of Participants With a Baseline Titre Less Than 1:10 Achieving Seroconversion After Vaccination
Description	The number of participants with a baseline titre less than 1:10 differed according to antibody assay (HI or MN) and is shown in the category titles accordingly. The total number of participants analysed includes all evaluable participants; however, the analysis is stratified by baseline titre and those participants with a baseline titre less than 1:10 are presented in this outcome measure while those with a baseline titre of 1:10 or more are presented in a separate outcome measure. Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination titre of 1:40 or more; or participants with a pre-vaccination 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 each vaccination

Outcome Measure Data

Analysis Population Description

The Evaluable Population comprised all randomised participants who received the first (or second, as appropriate) 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).

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	120	119
After the first vaccination - HI (N = 42, 49)	92.9 77.4%	83.7 69.8%
After the second vaccination - HI (N = 42, 47)	95.2 79.3%	93.6 78%
After the first vaccination - MN (N = 62, 73)	77.4 64.5%	74.0 61.7%
After the second vaccination - MN (N = 60, 71)	91.7 76.4%	87.3 72.8%

14. Secondary Outcome

Title	Percentage of Participants With a Baseline Titre Greater Than or Equal to 1:10 Achieving Seroconversion After Vaccination
Description	The number of participants with a baseline titre greater than or equal to 1:10 differed according to antibody assay (HI or MN) and is shown in the category titles accordingly. The total number of participants analysed includes all evaluable participants; however, the analysis is stratified by baseline titre and those participants with a baseline titre of 1:10 or more are presented in this outcome measure while those with a baseline titre less than 1:10 are presented in a separate outcome measure. Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre (ie, a significant increase in antibody titre after vaccination).
Time Frame	Before and 21 days after each vaccination

Outcome Measure Data

Analysis Population Description

The Evaluable Population comprised all randomised participants who received the 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).

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	120	119
After the first vaccination - HI (N = 78, 70)	64.1 53.4%	80.0 66.7%
After the second vaccination - HI (N = 75, 68)	74.7 62.3%	86.8 72.3%
After the first vaccination - MN (N = 58, 46)	77.6 64.7%	78.3 65.3%
After the second vaccination - MN (N = 57, 44)	82.5 68.8%	77.3 64.4%

15. Secondary Outcome

Title	GMFI in the HI Antibody Titre 180 Days After the Second Vaccination
Description	The GMFI in antibody titre was calculated by taking the anti-logs of the means of the log transformed fold-increases in the antibody titre 180 days after the second vaccination over the antibody titre 21 days after the second vaccination.
Time Frame	21 days and 180 days after the second vaccination

Outcome Measure Data

Analysis Population Description

The Evaluable Population 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).

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	115	111
Geometric Mean (95% Confidence Interval) [geometric mean fold increase]	0.49	0.42

16. Secondary Outcome

Title	Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More 180 Days After the Second Vaccination
Time Frame	180 days after the second vaccination

Outcome Measure Data

Analysis Population Description

The Evaluable Population 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).

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	115	111
Number (95% Confidence Interval) [percentage of participants]	95.7 79.8%	91.9 76.6%

17. Secondary Outcome

Title	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination
Description	Solicited AEs included AEs that were specifically sought for. Grade 3 solicited AE definitions: Prevented normal daily activities; Size > 100 mm for injection site redness, induration/swelling, and bruising.
Time Frame	From Day 0 to Day 6 after the first vaccination

Outcome Measure Data

Analysis Population Description

The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	120	120
Any local solicited AE	40.0 33.3%	49.2 41%
Any pain at injection site	20.8 17.3%	22.5 18.8%
Grade 3 pain at injection site	0 0%	0 0%
Any redness at injection site	0.8 0.7%	0.8 0.7%
Grade 3 redness at injection site	0 0%	0 0%
Any swelling/induration at injection site	9.2 7.7%	8.3 6.9%
Grade 3 swelling/induration at injection site	0 0%	0 0%
Any tenderness at injection site	30.8 25.7%	42.5 35.4%
Grade 3 tenderness at injection site	0 0%	0 0%
Any bruising at injection site	5.0 4.2%	4.2 3.5%
Grade 3 bruising at injection site	0 0%	0 0%

18. Secondary Outcome

Title	Duration of Solicited Local AEs After the First Vaccination
Description	Solicited AEs included AEs that were specifically sought for.
Time Frame	From Day 0 to Day 6 after the first vaccination and up to Day 20 after the first vaccination if AE is ongoing at Day 7

Outcome Measure Data

Analysis Population Description

The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	120	120
Pain at injection site	1.96 (2.423)	1.67 (1.240)
Redness at injection site	1.00 (NA)	1.00 (NA)
Swelling/induration at injection site	1.64 (0.809)	2.70 (2.263)
Tenderness at injection site	2.24 (1.862)	1.88 (1.078)
Bruising at injection site	5.83 (6.113)	4.40 (7.057)

19. Secondary Outcome

Title	Frequency and Intensity of Solicited Local AEs After the Second Vaccination
Description	Solicited AEs included AEs that were specifically sought for. Grade 3 solicited AE definitions: Prevented normal daily activities; Size > 100 mm for injection site redness, induration/swelling, and bruising.
Time Frame	From Day 0 to Day 6 after the second vaccination

Outcome Measure Data

Analysis Population Description

The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	119	119
Any local solicited AE	28.6 23.8%	42.9 35.8%
Any pain at injection site	11.8 9.8%	16.8 14%
Grade 3 pain at injection site	0 0%	0 0%
Any redness at injection site	1.7 1.4%	2.5 2.1%
Grade 3 redness at injection site	0 0%	0 0%
Any swelling/induration at injection site	3.4 2.8%	5.9 4.9%
Grade 3 swelling/induration at injection site	0 0%	0 0%
Any tenderness at injection site	21.8 18.2%	39.5 32.9%
Grade 3 tenderness at injection site	0 0%	0 0%
Any bruising at injection site	2.5 2.1%	3.4 2.8%
Grade 3 bruising at injection site	0 0%	0 0%

20. Secondary Outcome

Title	Duration of Solicited Local AEs After the Second Vaccination
Description	Solicited AEs included AEs that were specifically sought for.
Time Frame	From Day 0 to Day 6 after the second vaccination and up to Day 20 after the second vaccination if AE is ongoing at Day 7

Outcome Measure Data

Analysis Population Description

The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	119	119
Pain at injection site	1.50 (0.519)	2.40 (4.430)
Redness at injection site	6.00 (5.657)	1.67 (1.155)
Swelling/induration at injection site	1.75 (0.500)	1.43 (0.787)
Tenderness at injection site	1.62 (0.852)	2.11 (1.521)
Bruising at injection site	8.00 (5.196)	2.00 (0.707)

21. Secondary Outcome

Title	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination
Description	Solicited AEs included AEs that were specifically sought for. Grade 3 solicited AE definitions: Prevented normal daily activities; Temperature 102.2°F (39.0°C) or more for fevers.
Time Frame	From Day 0 to Day 6 after the first vaccination

Outcome Measure Data

Analysis Population Description

The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	120	120
Any solicited AE	37.5 31.3%	53.3 44.4%
Any headache	26.7 22.3%	37.5 31.3%
Grade 3 headache	0 0%	0 0%
Any malaise/feeling generally unwell	11.7 9.8%	22.5 18.8%
Grade 3 Malaise/feeling generally unwell	0.8 0.7%	0 0%
Any muscle ache (myalgia)	15.8 13.2%	19.2 16%
Grade 3 muscle ache (myalgia)	0.8 0.7%	0 0%
Any nausea	5.8 4.8%	8.3 6.9%
Grade 3 nausea	0.8 0.7%	0.8 0.7%
Any chills	0.8 0.7%	12.5 10.4%
Grade 3 chills	0 0%	0 0%
Any vomiting	0 0%	1.7 1.4%
Grade 3 vomiting	0 0%	0 0%
Any fever	5.0 4.2%	3.3 2.8%
Grade 3 fever	0 0%	0 0%

22. Secondary Outcome

Title	Duration of Solicited Systemic AEs After the First Vaccination
Description	Solicited AEs included AEs that were specifically sought for.
Time Frame	From Day 0 to Day 6 after the first vaccination and up to Day 20 after the first vaccination if AE is ongoing at Day 7

Outcome Measure Data

Analysis Population Description

The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	120	120
Headache	1.15 (0.432)	1.64 (1.419)
Malaise/feeling generally unwell	2.00 (1.328)	1.47 (1.134)
Muscle ache (myalgia)	2.24 (1.729)	1.67 (1.240)
Nausea	1.25 (0.707)	1.64 (1.286)
Chills	3.00 (NA)	1.38 (0.885)
Vomiting	NA (NA)	2.00 (1.414)
Fever	1.14 (0.378)	1.00 (0.000)

23. Secondary Outcome

Title	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination
Description	Solicited AEs included AEs that were specifically sought for. Grade 3 solicited AE definitions: Prevented normal daily activities; Temperature 102.2°F (39.0°C) or more for fevers.
Time Frame	From Day 0 to Day 6 after the second vaccination

Outcome Measure Data

Analysis Population Description

The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	119	119
Any solicited AE	19.3 16.1%	32.8 27.3%
Any headache	12.6 10.5%	21.8 18.2%
Grade 3 headache	0 0%	0 0%
Any malaise/feeling generally unwell	9.2 7.7%	15.1 12.6%
Grade 3 Malaise/feeling generally unwell	0.8 0.7%	0 0%
Any muscle ache (myalgia)	9.2 7.7%	11.8 9.8%
Grade 3 muscle ache (myalgia)	0 0%	0.8 0.7%
Any nausea	1.7 1.4%	4.2 3.5%
Grade 3 nausea	0 0%	0 0%
Any chills	0.8 0.7%	1.7 1.4%
Grade 3 chills	0 0%	0 0%
Any vomiting	0 0%	0 0%
Grade 3 vomiting	0 0%	0 0%
Any fever	0 0%	2.5 2.1%
Grade 3 fever	0 0%	0 0%

24. Secondary Outcome

Title	Duration of Solicited Systemic AEs After the Second Vaccination
Description	Solicited AEs included AEs that were specifically sought for.
Time Frame	From Day 0 to Day 6 after the second vaccination and up to Day 20 after the second vaccination if AE is ongoing at Day 7

Outcome Measure Data

Analysis Population Description

The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	119	119
Headache	1.19 (0.403)	1.58 (1.173)
Malaise/feeling generally unwell	1.64 (0.929)	2.10 (1.841)
Muscle ache (myalgia)	2.08 (2.275)	2.06 (1.611)
Nausea	2.00 (1.414)	1.29 (0.488)
Chills	2.00 (NA)	1.25 (0.500)
Vomiting	NA (NA)	NA (NA)
Fever	NA (NA)	1.33 (0.577)

25. Secondary Outcome

Title	Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)
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

Outcome Measure Data

Analysis Population Description

The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	120	120
At least one SAE	0.8 0.7%	0 0%
Related SAE	0 0%	0 0%
At least one AESI	0 0%	0 0%
Related AESI	0 0%	0 0%
At least one NOCI	2.5 2.1%	2.5 2.1%
Related NOCI	0.8 0.7%	1.7 1.4%

26. Secondary Outcome

Title	Frequency and Intensity of Unsolicited AEs
Description	Unsolicited AEs included AEs other than those specifically sought for. The grading definitions were: Mild (Grade 1): Symptoms were easily tolerated and did not interfere with daily activities. Moderate (Grade 2): Enough discomfort to cause some interference with daily activities. Severe (Grade 3): Incapacitating, with inability to work or do usual activities.
Time Frame	From Day 0 to Day 20 after vaccination; up to 180 days after the last vaccination for SAEs, AESIs, and NOCIs

Outcome Measure Data

Analysis Population Description

The Safety Population comprised all participants who received at least one dose of the vaccine and provided follow-up safety data.

Arm/Group Title	CSL425 (15 mcg)	CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
Measure Participants	120	120
All unsolicited AEs after the first dose	40.0 33.3%	35.0 29.2%
Grade 1 unsolicited AEs after the first dose	24.2 20.2%	15.8 13.2%
Grade 2 unsolicited AEs after the first dose	15.0 12.5%	15.0 12.5%
Grade 3 unsolicited AEs after the first dose	0.8 0.7%	4.2 3.5%
All unsolicited AEs after the second dose (n=119)	25.2 21%	28.6 23.8%
Total unsolicited AEs after doses 1 & 2	44.2 36.8%	45.8 38.2%
Total grade 1 unsolicited AEs after doses 1 & 2	25.0 20.8%	20.8 17.3%
Total grade 2 unsolicited AEs after doses 1 & 2	17.5 14.6%	20.0 16.7%
Total grade 3 unsolicited AEs after doses 1 & 2	1.7 1.4%	5.0 4.2%

Adverse Events

Time Frame	For SAEs: up to 180 days after the last vaccination. For Other AEs: solicited AEs: from Day 0 to Day 6 after each vaccination; unsolicited AEs: from Day 0 to Day 20 after each vaccination; up to 180 days after the last vaccination for AESIs and NOCIs.
Adverse Event Reporting Description	Unsolicited AEs presented in the organ system "General disorders" with a footnote of "MedDRA 12.1", were collected under the MedDRA System Organ Class (SOC) 'General disorders and administration site conditions'. Solicited AEs are presented in the organ system "General disorders" and were not collected under the MedDRA SOC.
Arm/Group Title	CSL425 (15 mcg)		CSL425 (30 mcg)
Arm/Group Description	15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21		30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21
All Cause Mortality
	CSL425 (15 mcg)		CSL425 (30 mcg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CSL425 (15 mcg)		CSL425 (30 mcg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/120 (0.8%)		0/120 (0%)
Nervous system disorders
Tension headache	1/120 (0.8%)	1	0/120 (0%)	0
Other (Not Including Serious) Adverse Events
	CSL425 (15 mcg)		CSL425 (30 mcg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	97/120 (80.8%)		99/120 (82.5%)
Ear and labyrinth disorders
Motion sickness	0/120 (0%)	0	2/120 (1.7%)	2
Endocrine disorders
Hypothyroidism	2/120 (1.7%)	2	1/120 (0.8%)	1
Gastrointestinal disorders
Diarrhoea	5/120 (4.2%)	5	2/120 (1.7%)	3
Toothache	3/120 (2.5%)	5	0/120 (0%)	0
Dyspepsia	2/120 (1.7%)	6	0/120 (0%)	0
Vomiting	0/120 (0%)	0	2/120 (1.7%)	2
General disorders
Fatigue	2/120 (1.7%)	2	3/120 (2.5%)	3
Pyrexia	4/120 (3.3%)	5	1/120 (0.8%)	1
Malaise	0/120 (0%)	0	2/120 (1.7%)	2
Pain at injection site	31/120 (25.8%)	39	36/120 (30%)	47
Redness at injection site	3/120 (2.5%)	3	4/120 (3.3%)	4
Swelling/Induration at injection site	13/120 (10.8%)	15	15/120 (12.5%)	17
Tenderness at injection site	47/120 (39.2%)	63	66/120 (55%)	99
Bruising at injection site	8/120 (6.7%)	9	9/120 (7.5%)	10
Headache	42/120 (35%)	55	52/120 (43.3%)	87
Malaise/feeling generally unwell	22/120 (18.3%)	32	37/120 (30.8%)	55
Muscle ache (myalgia)	26/120 (21.7%)	33	29/120 (24.2%)	43
Nausea	9/120 (7.5%)	10	12/120 (10%)	18
Chills	2/120 (1.7%)	2	16/120 (13.3%)	20
Vomiting	0/120 (0%)	0	2/120 (1.7%)	2
Fever	6/120 (5%)	7	6/120 (5%)	7
Immune system disorders
Seasonal allergy	4/120 (3.3%)	8	1/120 (0.8%)	1
Infections and infestations
Upper respiratory tract infection	5/120 (4.2%)	5	4/120 (3.3%)	4
Nasopharyngitis	3/120 (2.5%)	3	2/120 (1.7%)	2
Cystitis	0/120 (0%)	0	2/120 (1.7%)	2
Tooth infection	2/120 (1.7%)	2	0/120 (0%)	0
Diverticulitis	0/120 (0%)	0	2/120 (1.7%)	2
Musculoskeletal and connective tissue disorders
Back pain	7/120 (5.8%)	8	2/120 (1.7%)	2
Arthralgia	3/120 (2.5%)	5	3/120 (2.5%)	5
Myalgia	0/120 (0%)	0	3/120 (2.5%)	3
Neck pain	2/120 (1.7%)	2	2/120 (1.7%)	3
Nervous system disorders
Headache	20/120 (16.7%)	35	25/120 (20.8%)	44
Reproductive system and breast disorders
Dysmenorrhoea	0/120 (0%)	0	7/120 (5.8%)	9
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	5/120 (4.2%)	5	9/120 (7.5%)	10
Cough	3/120 (2.5%)	3	6/120 (5%)	7
Rhinorrhoea	1/120 (0.8%)	1	5/120 (4.2%)	5
Nasal congestion	4/120 (3.3%)	4	1/120 (0.8%)	1
Sneezing	2/120 (1.7%)	2	1/120 (0.8%)	1
Sinus congestion	2/120 (1.7%)	2	3/120 (2.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

CSL agreements and restrictions on publishing may vary with individual investigators; however, CSL will not prohibit any investigator from publishing. CSL supports the publication of results from all centers of a multi-center trial and generally requires that reports based on single-site data not precede the primary publication of the entire clinical trial.