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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Influenza Caused by the Novel Influenza A (H1N1) Virus

Intervention / Treatment
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* Biological: CSL425
* Biological: CSL425


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CSL425 (15 mcg)<br>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<br>* CSL's 2009 H1N1 Influenza Vaccine, thimerosal 0.01% (weight/volume)<br>|
| Experimental: CSL425 (30 mcg)<br>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<br>* CSL's 2009 H1N1 Influenza Vaccine, thimerosal 0.01% (weight/volume)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Before and 21 days after the first vaccination | 
| HI and MN Antibody Titre Seroconversion Rate 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. | Before and 21 days after the second vaccination | 
| 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. | Before and 21 days after the first vaccination | 
| 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. | Before and 21 days after the second vaccination | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HI and MN Antibody Titre Seroconversion Rate After the First Vaccination by Age Group | 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. | Before and 21 days after the first vaccination | 
| HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination by Age Group | 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. | Before and 21 days after the second vaccination | 
| 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. | Before and 21 days after the first vaccination | 
| GMFI in the HI and MN Antibody Titre After the Second 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. | Before and 21 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 | Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years. | 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 by Age Group | Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years. | 21 days after the second vaccination | 
| 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. | Before and 21 days after each vaccination | 
| 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). | Before and 21 days after each vaccination | 
| 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. | 21 days and 180 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 | 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. | From Day 0 to Day 6 after the first vaccination | 
| Duration of Solicited Local AEs After the First Vaccination | Solicited AEs included AEs that were specifically sought for. | 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 | 
| Frequency and Intensity of Solicited Local AEs 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. | From Day 0 to Day 6 after the second vaccination | 
| Duration of Solicited Local AEs After the Second Vaccination | Solicited AEs included AEs that were specifically sought for. | 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 | 
| 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. | From Day 0 to Day 6 after the first vaccination | 
| Duration of Solicited Systemic AEs After the First Vaccination | Solicited AEs included AEs that were specifically sought for. | 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 | 
| 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. | From Day 0 to Day 6 after the second vaccination | 
| Duration of Solicited Systemic AEs After the Second Vaccination | Solicited AEs included AEs that were specifically sought for. | 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 | 
| 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). | Up to 180 days after the last vaccination | 
| 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. | From Day 0 to Day 20 after vaccination; up to 180 days after the last vaccination for SAEs, AESIs, and NOCIs |