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

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.

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00938639

Enrollment

240

Registered

2009-07-14

Start date

2009-07-31

Completion date

2010-03-31

Last updated

2018-06-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Influenza Caused by the Novel Influenza A (H1N1) Virus

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.

Interventions

BIOLOGICALCSL425

CSL's 2009 H1N1 Influenza Vaccine, thimerosal 0.01% (weight/volume)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 64 Years

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.

Design outcomes

Primary

Measure	Time frame	Description
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.
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.
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.
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.
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	—
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

Measure	Time frame	Description
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.
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).
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.
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	—
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.

Countries

Australia

Participant flow

Participants by arm

Arm	Count
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	120
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	120
Total	240

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Family issues	1	1
Overall Study	Lost to Follow-up	1	2
Overall Study	Moved away from study area	0	1
Overall Study	Participant noncompliance	1	0

Baseline characteristics

Characteristic	CSL425 (15 mcg)	CSL425 (30 mcg)	Total
Age, Continuous	44.6 years STANDARD_DEVIATION 15.12	42.9 years STANDARD_DEVIATION 15.39	43.7 years STANDARD_DEVIATION 15.25
Sex: Female, Male Female	67 Participants	67 Participants	134 Participants
Sex: Female, Male Male	53 Participants	53 Participants	106 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	97 / 120	99 / 120
serious Total, serious adverse events	1 / 120	0 / 120

Outcome results

Primary

Geometric Mean Fold Increase (GMFI) in the HI and MN Antibody Titre 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.

Time frame: Before and 21 days after the first vaccination

Population: 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	Measure	Group	Value (GEOMETRIC_MEAN)
CSL425 (15 mcg)	Geometric Mean Fold Increase (GMFI) in the HI and MN Antibody Titre After the First Vaccination	GMFI - HI	11.83 geometric mean fold increase
CSL425 (15 mcg)	Geometric Mean Fold Increase (GMFI) in the HI and MN Antibody Titre After the First Vaccination	GMFI - MN	24.83 geometric mean fold increase
CSL425 (30 mcg)	Geometric Mean Fold Increase (GMFI) in the HI and MN Antibody Titre After the First Vaccination	GMFI - HI	19.54 geometric mean fold increase
CSL425 (30 mcg)	Geometric Mean Fold Increase (GMFI) in the HI and MN Antibody Titre After the First Vaccination	GMFI - MN	39.70 geometric mean fold increase

Primary

GMFI in the HI and MN Antibody Titer 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.

Time frame: Before and 21 days after the second vaccination

Population: 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	Measure	Group	Value (GEOMETRIC_MEAN)
CSL425 (15 mcg)	GMFI in the HI and MN Antibody Titer After the Second Vaccination	GMFI - MN	32.30 geometric mean fold increase
CSL425 (15 mcg)	GMFI in the HI and MN Antibody Titer After the Second Vaccination	GMFI - HI	16.00 geometric mean fold increase
CSL425 (30 mcg)	GMFI in the HI and MN Antibody Titer After the Second Vaccination	GMFI - HI	23.30 geometric mean fold increase
CSL425 (30 mcg)	GMFI in the HI and MN Antibody Titer After the Second Vaccination	GMFI - MN	46.50 geometric mean fold increase

Primary

Haemagglutination Inhibition (HI) and Microneutralisation (MN) Antibody Titre Seroconversion Rate 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.

Time frame: Before and 21 days after the first vaccination

Arm	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	Haemagglutination Inhibition (HI) and Microneutralisation (MN) Antibody Titre Seroconversion Rate After the First Vaccination	Seroconversion rate - HI	74.2 percentage of participants
CSL425 (15 mcg)	Haemagglutination Inhibition (HI) and Microneutralisation (MN) Antibody Titre Seroconversion Rate After the First Vaccination	Seroconversion rate - MN	77.5 percentage of participants
CSL425 (30 mcg)	Haemagglutination Inhibition (HI) and Microneutralisation (MN) Antibody Titre Seroconversion Rate After the First Vaccination	Seroconversion rate - HI	81.5 percentage of participants
CSL425 (30 mcg)	Haemagglutination Inhibition (HI) and Microneutralisation (MN) Antibody Titre Seroconversion Rate After the First Vaccination	Seroconversion rate - MN	75.6 percentage of participants

Primary

HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination

Time frame: Before and 21 days after the second vaccination

Arm	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination	Seroconversion rate - HI	82.1 percentage of participants
CSL425 (15 mcg)	HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination	Seroconversion rate - MN	87.2 percentage of participants
CSL425 (30 mcg)	HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination	Seroconversion rate - MN	83.5 percentage of participants
CSL425 (30 mcg)	HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination	Seroconversion rate - HI	89.6 percentage of participants

Primary

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

Arm	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination	Participants with HI titer ≥ 1:40	95.0 percentage of participants
CSL425 (15 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination	Participants with MN titer ≥ 1:40	88.3 percentage of participants
CSL425 (30 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination	Participants with HI titer ≥ 1:40	89.1 percentage of participants
CSL425 (30 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination	Participants with MN titer ≥ 1:40	83.2 percentage of participants

Primary

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

Arm	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination	Participants with MN titer ≥ 1:40	95.7 percentage of participants
CSL425 (15 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination	Participants with HI titer ≥ 1:40	98.3 percentage of participants
CSL425 (30 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination	Participants with MN titer ≥ 1:40	92.2 percentage of participants
CSL425 (30 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination	Participants with HI titer ≥ 1:40	96.5 percentage of participants

Secondary

Duration of Solicited Local AEs After the First Vaccination

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
CSL425 (15 mcg)	Duration of Solicited Local AEs After the First Vaccination	Redness at injection site	1.00 days	—
CSL425 (15 mcg)	Duration of Solicited Local AEs After the First Vaccination	Tenderness at injection site	2.24 days	Standard Deviation 1.862
CSL425 (15 mcg)	Duration of Solicited Local AEs After the First Vaccination	Swelling/induration at injection site	1.64 days	Standard Deviation 0.809
CSL425 (15 mcg)	Duration of Solicited Local AEs After the First Vaccination	Bruising at injection site	5.83 days	Standard Deviation 6.113
CSL425 (15 mcg)	Duration of Solicited Local AEs After the First Vaccination	Pain at injection site	1.96 days	Standard Deviation 2.423
CSL425 (30 mcg)	Duration of Solicited Local AEs After the First Vaccination	Bruising at injection site	4.40 days	Standard Deviation 7.057
CSL425 (30 mcg)	Duration of Solicited Local AEs After the First Vaccination	Pain at injection site	1.67 days	Standard Deviation 1.24
CSL425 (30 mcg)	Duration of Solicited Local AEs After the First Vaccination	Redness at injection site	1.00 days	—
CSL425 (30 mcg)	Duration of Solicited Local AEs After the First Vaccination	Swelling/induration at injection site	2.70 days	Standard Deviation 2.263
CSL425 (30 mcg)	Duration of Solicited Local AEs After the First Vaccination	Tenderness at injection site	1.88 days	Standard Deviation 1.078

Secondary

Duration of Solicited Local AEs After the Second Vaccination

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
CSL425 (15 mcg)	Duration of Solicited Local AEs After the Second Vaccination	Redness at injection site	6.00 days	Standard Deviation 5.657
CSL425 (15 mcg)	Duration of Solicited Local AEs After the Second Vaccination	Tenderness at injection site	1.62 days	Standard Deviation 0.852
CSL425 (15 mcg)	Duration of Solicited Local AEs After the Second Vaccination	Swelling/induration at injection site	1.75 days	Standard Deviation 0.5
CSL425 (15 mcg)	Duration of Solicited Local AEs After the Second Vaccination	Bruising at injection site	8.00 days	Standard Deviation 5.196
CSL425 (15 mcg)	Duration of Solicited Local AEs After the Second Vaccination	Pain at injection site	1.50 days	Standard Deviation 0.519
CSL425 (30 mcg)	Duration of Solicited Local AEs After the Second Vaccination	Bruising at injection site	2.00 days	Standard Deviation 0.707
CSL425 (30 mcg)	Duration of Solicited Local AEs After the Second Vaccination	Pain at injection site	2.40 days	Standard Deviation 4.43
CSL425 (30 mcg)	Duration of Solicited Local AEs After the Second Vaccination	Redness at injection site	1.67 days	Standard Deviation 1.155
CSL425 (30 mcg)	Duration of Solicited Local AEs After the Second Vaccination	Swelling/induration at injection site	1.43 days	Standard Deviation 0.787
CSL425 (30 mcg)	Duration of Solicited Local AEs After the Second Vaccination	Tenderness at injection site	2.11 days	Standard Deviation 1.521

Secondary

Duration of Solicited Systemic AEs After the First Vaccination

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
CSL425 (15 mcg)	Duration of Solicited Systemic AEs After the First Vaccination	Vomiting	NA days	—
CSL425 (15 mcg)	Duration of Solicited Systemic AEs After the First Vaccination	Fever	1.14 days	Standard Deviation 0.378
CSL425 (15 mcg)	Duration of Solicited Systemic AEs After the First Vaccination	Headache	1.15 days	Standard Deviation 0.432
CSL425 (15 mcg)	Duration of Solicited Systemic AEs After the First Vaccination	Malaise/feeling generally unwell	2.00 days	Standard Deviation 1.328
CSL425 (15 mcg)	Duration of Solicited Systemic AEs After the First Vaccination	Muscle ache (myalgia)	2.24 days	Standard Deviation 1.729
CSL425 (15 mcg)	Duration of Solicited Systemic AEs After the First Vaccination	Nausea	1.25 days	Standard Deviation 0.707
CSL425 (15 mcg)	Duration of Solicited Systemic AEs After the First Vaccination	Chills	3.00 days	—
CSL425 (30 mcg)	Duration of Solicited Systemic AEs After the First Vaccination	Vomiting	2.00 days	Standard Deviation 1.414
CSL425 (30 mcg)	Duration of Solicited Systemic AEs After the First Vaccination	Muscle ache (myalgia)	1.67 days	Standard Deviation 1.24
CSL425 (30 mcg)	Duration of Solicited Systemic AEs After the First Vaccination	Fever	1.00 days	Standard Deviation 0
CSL425 (30 mcg)	Duration of Solicited Systemic AEs After the First Vaccination	Chills	1.38 days	Standard Deviation 0.885
CSL425 (30 mcg)	Duration of Solicited Systemic AEs After the First Vaccination	Headache	1.64 days	Standard Deviation 1.419
CSL425 (30 mcg)	Duration of Solicited Systemic AEs After the First Vaccination	Nausea	1.64 days	Standard Deviation 1.286
CSL425 (30 mcg)	Duration of Solicited Systemic AEs After the First Vaccination	Malaise/feeling generally unwell	1.47 days	Standard Deviation 1.134

Secondary

Duration of Solicited Systemic AEs After the Second Vaccination

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
CSL425 (15 mcg)	Duration of Solicited Systemic AEs After the Second Vaccination	Vomiting	NA days	—
CSL425 (15 mcg)	Duration of Solicited Systemic AEs After the Second Vaccination	Malaise/feeling generally unwell	1.64 days	Standard Deviation 0.929
CSL425 (15 mcg)	Duration of Solicited Systemic AEs After the Second Vaccination	Muscle ache (myalgia)	2.08 days	Standard Deviation 2.275
CSL425 (15 mcg)	Duration of Solicited Systemic AEs After the Second Vaccination	Fever	NA days	—
CSL425 (15 mcg)	Duration of Solicited Systemic AEs After the Second Vaccination	Nausea	2.00 days	Standard Deviation 1.414
CSL425 (15 mcg)	Duration of Solicited Systemic AEs After the Second Vaccination	Chills	2.00 days	—
CSL425 (15 mcg)	Duration of Solicited Systemic AEs After the Second Vaccination	Headache	1.19 days	Standard Deviation 0.403
CSL425 (30 mcg)	Duration of Solicited Systemic AEs After the Second Vaccination	Nausea	1.29 days	Standard Deviation 0.488
CSL425 (30 mcg)	Duration of Solicited Systemic AEs After the Second Vaccination	Headache	1.58 days	Standard Deviation 1.173
CSL425 (30 mcg)	Duration of Solicited Systemic AEs After the Second Vaccination	Fever	1.33 days	Standard Deviation 0.577
CSL425 (30 mcg)	Duration of Solicited Systemic AEs After the Second Vaccination	Malaise/feeling generally unwell	2.10 days	Standard Deviation 1.841
CSL425 (30 mcg)	Duration of Solicited Systemic AEs After the Second Vaccination	Chills	1.25 days	Standard Deviation 0.5
CSL425 (30 mcg)	Duration of Solicited Systemic AEs After the Second Vaccination	Muscle ache (myalgia)	2.06 days	Standard Deviation 1.611
CSL425 (30 mcg)	Duration of Solicited Systemic AEs After the Second Vaccination	Vomiting	NA days	—

Secondary

Frequency and Intensity of Solicited Local Adverse Events (AEs) 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.

Time frame: From Day 0 to Day 6 after the first vaccination

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

Arm	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Any local solicited AE	40.0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Any pain at injection site	20.8 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Any tenderness at injection site	30.8 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Grade 3 tenderness at injection site	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Any bruising at injection site	5.0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Grade 3 pain at injection site	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Any redness at injection site	0.8 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Grade 3 redness at injection site	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Any swelling/induration at injection site	9.2 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Grade 3 swelling/induration at injection site	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Grade 3 bruising at injection site	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Grade 3 bruising at injection site	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Any local solicited AE	49.2 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Any redness at injection site	0.8 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Any pain at injection site	22.5 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Grade 3 swelling/induration at injection site	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Any tenderness at injection site	42.5 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Grade 3 redness at injection site	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Grade 3 tenderness at injection site	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Any bruising at injection site	4.2 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Any swelling/induration at injection site	8.3 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Grade 3 pain at injection site	0 percentage of participants

Secondary

Frequency and Intensity of Solicited Local AEs After the Second Vaccination

Time frame: From Day 0 to Day 6 after the second vaccination

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

Arm	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Any redness at injection site	1.7 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Grade 3 swelling/induration at injection site	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Grade 3 pain at injection site	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Any tenderness at injection site	21.8 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Grade 3 redness at injection site	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Any pain at injection site	11.8 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Any bruising at injection site	2.5 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Any swelling/induration at injection site	3.4 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Grade 3 bruising at injection site	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Grade 3 tenderness at injection site	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Any local solicited AE	28.6 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Grade 3 bruising at injection site	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Any local solicited AE	42.9 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Any pain at injection site	16.8 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Grade 3 pain at injection site	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Any redness at injection site	2.5 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Grade 3 redness at injection site	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Any swelling/induration at injection site	5.9 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Grade 3 swelling/induration at injection site	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Any tenderness at injection site	39.5 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Grade 3 tenderness at injection site	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Any bruising at injection site	3.4 percentage of participants

Secondary

Frequency and Intensity of Solicited Systemic AEs 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.

Time frame: From Day 0 to Day 6 after the first vaccination

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

Arm	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any vomiting	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any headache	26.7 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Grade 3 vomiting	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any solicited AE	37.5 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any muscle ache (myalgia)	15.8 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Grade 3 nausea	0.8 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any malaise/feeling generally unwell	11.7 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any chills	0.8 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Grade 3 muscle ache (myalgia)	0.8 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Grade 3 chills	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Grade 3 headache	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any fever	5.0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any nausea	5.8 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Grade 3 fever	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Grade 3 Malaise/feeling generally unwell	0.8 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Grade 3 fever	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any headache	37.5 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Grade 3 headache	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any malaise/feeling generally unwell	22.5 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Grade 3 Malaise/feeling generally unwell	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any muscle ache (myalgia)	19.2 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Grade 3 muscle ache (myalgia)	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Grade 3 chills	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any vomiting	1.7 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any nausea	8.3 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Grade 3 nausea	0.8 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any chills	12.5 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Grade 3 vomiting	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any fever	3.3 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Any solicited AE	53.3 percentage of participants

Secondary

Frequency and Intensity of Solicited Systemic AEs 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.

Time frame: From Day 0 to Day 6 after the second vaccination

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

Arm	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any solicited AE	19.3 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any malaise/feeling generally unwell	9.2 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Grade 3 Malaise/feeling generally unwell	0.8 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any muscle ache (myalgia)	9.2 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any vomiting	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any headache	12.6 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Grade 3 headache	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Grade 3 muscle ache (myalgia)	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any nausea	1.7 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Grade 3 nausea	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any chills	0.8 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Grade 3 chills	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Grade 3 vomiting	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any fever	0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Grade 3 fever	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any muscle ache (myalgia)	11.8 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any fever	2.5 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any malaise/feeling generally unwell	15.1 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Grade 3 muscle ache (myalgia)	0.8 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Grade 3 Malaise/feeling generally unwell	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any chills	1.7 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Grade 3 chills	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any nausea	4.2 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any vomiting	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Grade 3 fever	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any solicited AE	32.8 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Grade 3 vomiting	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Any headache	21.8 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Grade 3 nausea	0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Grade 3 headache	0 percentage of participants

Secondary

Frequency and Intensity of Unsolicited AEs

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

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

Arm	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	Frequency and Intensity of Unsolicited AEs	Total grade 3 unsolicited AEs after doses 1 & 2	1.7 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Unsolicited AEs	Grade 2 unsolicited AEs after the first dose	15.0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Unsolicited AEs	Grade 3 unsolicited AEs after the first dose	0.8 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Unsolicited AEs	Total grade 1 unsolicited AEs after doses 1 & 2	25.0 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Unsolicited AEs	Total grade 2 unsolicited AEs after doses 1 & 2	17.5 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Unsolicited AEs	Grade 1 unsolicited AEs after the first dose	24.2 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Unsolicited AEs	All unsolicited AEs after the second dose (n=119)	25.2 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Unsolicited AEs	Total unsolicited AEs after doses 1 & 2	44.2 percentage of participants
CSL425 (15 mcg)	Frequency and Intensity of Unsolicited AEs	All unsolicited AEs after the first dose	40.0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Unsolicited AEs	Total unsolicited AEs after doses 1 & 2	45.8 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Unsolicited AEs	All unsolicited AEs after the first dose	35.0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Unsolicited AEs	Grade 1 unsolicited AEs after the first dose	15.8 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Unsolicited AEs	Total grade 2 unsolicited AEs after doses 1 & 2	20.0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Unsolicited AEs	Grade 2 unsolicited AEs after the first dose	15.0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Unsolicited AEs	Total grade 3 unsolicited AEs after doses 1 & 2	5.0 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Unsolicited AEs	Grade 3 unsolicited AEs after the first dose	4.2 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Unsolicited AEs	All unsolicited AEs after the second dose (n=119)	28.6 percentage of participants
CSL425 (30 mcg)	Frequency and Intensity of Unsolicited AEs	Total grade 1 unsolicited AEs after doses 1 & 2	20.8 percentage of participants

Secondary

GMFI in the HI and MN Antibody Titre After the First Vaccination by Age Group

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

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
CSL425 (15 mcg)	GMFI in the HI and MN Antibody Titre After the First Vaccination by Age Group	GMFI - HI	15.13 geometric mean fold increase
CSL425 (15 mcg)	GMFI in the HI and MN Antibody Titre After the First Vaccination by Age Group	GMFI - MN	36.73 geometric mean fold increase
CSL425 (30 mcg)	GMFI in the HI and MN Antibody Titre After the First Vaccination by Age Group	GMFI - MN	17.21 geometric mean fold increase
CSL425 (30 mcg)	GMFI in the HI and MN Antibody Titre After the First Vaccination by Age Group	GMFI - HI	9.39 geometric mean fold increase
CSL425 (30 mcg), Adult	GMFI in the HI and MN Antibody Titre After the First Vaccination by Age Group	GMFI - HI	25.79 geometric mean fold increase
CSL425 (30 mcg), Adult	GMFI in the HI and MN Antibody Titre After the First Vaccination by Age Group	GMFI - MN	54.91 geometric mean fold increase
CSL425 (30 mcg), Older Adult	GMFI in the HI and MN Antibody Titre After the First Vaccination by Age Group	GMFI - HI	14.60 geometric mean fold increase
CSL425 (30 mcg), Older Adult	GMFI in the HI and MN Antibody Titre After the First Vaccination by Age Group	GMFI - MN	28.22 geometric mean fold increase

Secondary

GMFI in the HI and MN Antibody Titre After the Second Vaccination by Age Group

Time frame: Before and 21 days after the second vaccination

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
CSL425 (15 mcg)	GMFI in the HI and MN Antibody Titre After the Second Vaccination by Age Group	GMFI - MN	37.95 geometric mean fold increase
CSL425 (15 mcg)	GMFI in the HI and MN Antibody Titre After the Second Vaccination by Age Group	GMFI - HI	18.00 geometric mean fold increase
CSL425 (30 mcg)	GMFI in the HI and MN Antibody Titre After the Second Vaccination by Age Group	GMFI - HI	14.41 geometric mean fold increase
CSL425 (30 mcg)	GMFI in the HI and MN Antibody Titre After the Second Vaccination by Age Group	GMFI - MN	28.00 geometric mean fold increase
CSL425 (30 mcg), Adult	GMFI in the HI and MN Antibody Titre After the Second Vaccination by Age Group	GMFI - HI	26.01 geometric mean fold increase
CSL425 (30 mcg), Adult	GMFI in the HI and MN Antibody Titre After the Second Vaccination by Age Group	GMFI - MN	55.79 geometric mean fold increase
CSL425 (30 mcg), Older Adult	GMFI in the HI and MN Antibody Titre After the Second Vaccination by Age Group	GMFI - MN	38.63 geometric mean fold increase
CSL425 (30 mcg), Older Adult	GMFI in the HI and MN Antibody Titre After the Second Vaccination by Age Group	GMFI - HI	20.82 geometric mean fold increase

Secondary

GMFI in the HI Antibody Titre 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.

Time frame: 21 days and 180 days after the second vaccination

Population: 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	Measure	Value (GEOMETRIC_MEAN)
CSL425 (15 mcg)	GMFI in the HI Antibody Titre 180 Days After the Second Vaccination	0.49 geometric mean fold increase
CSL425 (30 mcg)	GMFI in the HI Antibody Titre 180 Days After the Second Vaccination	0.42 geometric mean fold increase

Secondary

HI and MN Antibody Titre Seroconversion Rate After the First Vaccination by Age Group

Time frame: Before and 21 days after the first vaccination

Arm	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	HI and MN Antibody Titre Seroconversion Rate After the First Vaccination by Age Group	Seroconversion rate - HI	77.6 percentage of participants
CSL425 (15 mcg)	HI and MN Antibody Titre Seroconversion Rate After the First Vaccination by Age Group	Seroconversion rate - MN	82.8 percentage of participants
CSL425 (30 mcg)	HI and MN Antibody Titre Seroconversion Rate After the First Vaccination by Age Group	Seroconversion rate - MN	72.6 percentage of participants
CSL425 (30 mcg)	HI and MN Antibody Titre Seroconversion Rate After the First Vaccination by Age Group	Seroconversion rate - HI	71.0 percentage of participants
CSL425 (30 mcg), Adult	HI and MN Antibody Titre Seroconversion Rate After the First Vaccination by Age Group	Seroconversion rate - HI	85.2 percentage of participants
CSL425 (30 mcg), Adult	HI and MN Antibody Titre Seroconversion Rate After the First Vaccination by Age Group	Seroconversion rate - MN	83.6 percentage of participants
CSL425 (30 mcg), Older Adult	HI and MN Antibody Titre Seroconversion Rate After the First Vaccination by Age Group	Seroconversion rate - HI	77.6 percentage of participants
CSL425 (30 mcg), Older Adult	HI and MN Antibody Titre Seroconversion Rate After the First Vaccination by Age Group	Seroconversion rate - MN	67.2 percentage of participants

Secondary

HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination by Age Group

Time frame: Before and 21 days after the second vaccination

Arm	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination by Age Group	Seroconversion rate - HI	83.6 percentage of participants
CSL425 (15 mcg)	HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination by Age Group	Seroconversion rate - MN	89.1 percentage of participants
CSL425 (30 mcg)	HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination by Age Group	Seroconversion rate - MN	85.5 percentage of participants
CSL425 (30 mcg)	HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination by Age Group	Seroconversion rate - HI	80.6 percentage of participants
CSL425 (30 mcg), Adult	HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination by Age Group	Seroconversion rate - HI	87.9 percentage of participants
CSL425 (30 mcg), Adult	HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination by Age Group	Seroconversion rate - MN	86.2 percentage of participants
CSL425 (30 mcg), Older Adult	HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination by Age Group	Seroconversion rate - HI	91.2 percentage of participants
CSL425 (30 mcg), Older Adult	HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination by Age Group	Seroconversion rate - MN	80.7 percentage of participants

Secondary

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

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

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

Arm	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)	At least one AESI	0 percentage of participants
CSL425 (15 mcg)	Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)	Related AESI	0 percentage of participants
CSL425 (15 mcg)	Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)	At least one NOCI	2.5 percentage of participants
CSL425 (15 mcg)	Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)	Related NOCI	0.8 percentage of participants
CSL425 (15 mcg)	Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)	Related SAE	0 percentage of participants
CSL425 (15 mcg)	Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)	At least one SAE	0.8 percentage of participants
CSL425 (30 mcg)	Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)	Related SAE	0 percentage of participants
CSL425 (30 mcg)	Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)	At least one AESI	0 percentage of participants
CSL425 (30 mcg)	Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)	Related NOCI	1.7 percentage of participants
CSL425 (30 mcg)	Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)	Related AESI	0 percentage of participants
CSL425 (30 mcg)	Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)	At least one SAE	0 percentage of participants
CSL425 (30 mcg)	Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)	At least one NOCI	2.5 percentage of participants

Secondary

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

Arm	Measure	Value (NUMBER)
CSL425 (15 mcg)	Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More 180 Days After the Second Vaccination	95.7 percentage of participants
CSL425 (30 mcg)	Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More 180 Days After the Second Vaccination	91.9 percentage of participants

Secondary

Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination by Age Group

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

Arm	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination by Age Group	Participants with HI titer ≥ 1:40	96.6 percentage of participants
CSL425 (15 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination by Age Group	Participants with MN titer ≥ 1:40	94.8 percentage of participants
CSL425 (30 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination by Age Group	Participants with MN titer ≥ 1:40	82.3 percentage of participants
CSL425 (30 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination by Age Group	Participants with HI titer ≥ 1:40	93.5 percentage of participants
CSL425 (30 mcg), Adult	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination by Age Group	Participants with HI titer ≥ 1:40	98.4 percentage of participants
CSL425 (30 mcg), Adult	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination by Age Group	Participants with MN titer ≥ 1:40	95.1 percentage of participants
CSL425 (30 mcg), Older Adult	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination by Age Group	Participants with HI titer ≥ 1:40	79.3 percentage of participants
CSL425 (30 mcg), Older Adult	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination by Age Group	Participants with MN titer ≥ 1:40	70.7 percentage of participants

Secondary

Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination by Age Group

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

Arm	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination by Age Group	Participants with MN titer ≥ 1:40	100.0 percentage of participants
CSL425 (15 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination by Age Group	Participants with HI titer ≥ 1:40	98.2 percentage of participants
CSL425 (30 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination by Age Group	Participants with MN titer ≥ 1:40	91.9 percentage of participants
CSL425 (30 mcg)	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination by Age Group	Participants with HI titer ≥ 1:40	98.4 percentage of participants
CSL425 (30 mcg), Adult	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination by Age Group	Participants with HI titer ≥ 1:40	100.0 percentage of participants
CSL425 (30 mcg), Adult	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination by Age Group	Participants with MN titer ≥ 1:40	100.0 percentage of participants
CSL425 (30 mcg), Older Adult	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination by Age Group	Participants with MN titer ≥ 1:40	84.2 percentage of participants
CSL425 (30 mcg), Older Adult	Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination by Age Group	Participants with HI titer ≥ 1:40	93.0 percentage of participants

Secondary

Percentage of Participants With a Baseline Titre Greater Than or Equal to 1:10 Achieving Seroconversion After 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).

Time frame: Before and 21 days after each vaccination

Population: 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	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	Percentage of Participants With a Baseline Titre Greater Than or Equal to 1:10 Achieving Seroconversion After Vaccination	After the first vaccination - HI (N = 78, 70)	64.1 percentage of participants
CSL425 (15 mcg)	Percentage of Participants With a Baseline Titre Greater Than or Equal to 1:10 Achieving Seroconversion After Vaccination	After the second vaccination - HI (N = 75, 68)	74.7 percentage of participants
CSL425 (15 mcg)	Percentage of Participants With a Baseline Titre Greater Than or Equal to 1:10 Achieving Seroconversion After Vaccination	After the first vaccination - MN (N = 58, 46)	77.6 percentage of participants
CSL425 (15 mcg)	Percentage of Participants With a Baseline Titre Greater Than or Equal to 1:10 Achieving Seroconversion After Vaccination	After the second vaccination - MN (N = 57, 44)	82.5 percentage of participants
CSL425 (30 mcg)	Percentage of Participants With a Baseline Titre Greater Than or Equal to 1:10 Achieving Seroconversion After Vaccination	After the second vaccination - MN (N = 57, 44)	77.3 percentage of participants
CSL425 (30 mcg)	Percentage of Participants With a Baseline Titre Greater Than or Equal to 1:10 Achieving Seroconversion After Vaccination	After the first vaccination - HI (N = 78, 70)	80.0 percentage of participants
CSL425 (30 mcg)	Percentage of Participants With a Baseline Titre Greater Than or Equal to 1:10 Achieving Seroconversion After Vaccination	After the second vaccination - HI (N = 75, 68)	86.8 percentage of participants
CSL425 (30 mcg)	Percentage of Participants With a Baseline Titre Greater Than or Equal to 1:10 Achieving Seroconversion After Vaccination	After the first vaccination - MN (N = 58, 46)	78.3 percentage of participants

Secondary

Percentage of Participants With a Baseline Titre Less Than 1:10 Achieving Seroconversion After 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.

Time frame: Before and 21 days after each vaccination

Population: 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	Measure	Group	Value (NUMBER)
CSL425 (15 mcg)	Percentage of Participants With a Baseline Titre Less Than 1:10 Achieving Seroconversion After Vaccination	After the first vaccination - MN (N = 62, 73)	77.4 percentage of participants
CSL425 (15 mcg)	Percentage of Participants With a Baseline Titre Less Than 1:10 Achieving Seroconversion After Vaccination	After the first vaccination - HI (N = 42, 49)	92.9 percentage of participants
CSL425 (15 mcg)	Percentage of Participants With a Baseline Titre Less Than 1:10 Achieving Seroconversion After Vaccination	After the second vaccination - MN (N = 60, 71)	91.7 percentage of participants
CSL425 (15 mcg)	Percentage of Participants With a Baseline Titre Less Than 1:10 Achieving Seroconversion After Vaccination	After the second vaccination - HI (N = 42, 47)	95.2 percentage of participants
CSL425 (30 mcg)	Percentage of Participants With a Baseline Titre Less Than 1:10 Achieving Seroconversion After Vaccination	After the second vaccination - MN (N = 60, 71)	87.3 percentage of participants
CSL425 (30 mcg)	Percentage of Participants With a Baseline Titre Less Than 1:10 Achieving Seroconversion After Vaccination	After the first vaccination - MN (N = 62, 73)	74.0 percentage of participants
CSL425 (30 mcg)	Percentage of Participants With a Baseline Titre Less Than 1:10 Achieving Seroconversion After Vaccination	After the second vaccination - HI (N = 42, 47)	93.6 percentage of participants
CSL425 (30 mcg)	Percentage of Participants With a Baseline Titre Less Than 1:10 Achieving Seroconversion After Vaccination	After the first vaccination - HI (N = 42, 49)	83.7 percentage of participants

Source: ClinicalTrials.gov · Data processed: Apr 2, 2026

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

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

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

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

Haemagglutination Inhibition (HI) and Microneutralisation (MN) Antibody Titre Seroconversion Rate After the First Vaccination

HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination

Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination

Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination

Duration of Solicited Local AEs After the First Vaccination

Duration of Solicited Local AEs After the Second Vaccination

Duration of Solicited Systemic AEs After the First Vaccination

Duration of Solicited Systemic AEs After the Second Vaccination

Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination

Frequency and Intensity of Solicited Local AEs After the Second Vaccination

Frequency and Intensity of Solicited Systemic AEs After the First Vaccination

Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination

Frequency and Intensity of Unsolicited AEs

GMFI in the HI and MN Antibody Titre After the First Vaccination by Age Group

GMFI in the HI and MN Antibody Titre After the Second Vaccination by Age Group

GMFI in the HI Antibody Titre 180 Days After the Second Vaccination

HI and MN Antibody Titre Seroconversion Rate After the First Vaccination by Age Group

HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination by Age Group

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

Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More 180 Days After the Second Vaccination

Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination by Age Group

Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination by Age Group

Percentage of Participants With a Baseline Titre Greater Than or Equal to 1:10 Achieving Seroconversion After Vaccination

Percentage of Participants With a Baseline Titre Less Than 1:10 Achieving Seroconversion After Vaccination