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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether CSL425 is a safe and effective vaccine for eliciting an immune response to H1N1 influenza in healthy children.

Official Title
-----------------
A Phase II, Multicentre, Randomised, Observer-blind Study to Evaluate the Immunogenicity, Safety and Tolerability of CSL's 2009 H1N1 Influenza Vaccine (CSL425) in Healthy Children Aged >= 6 Months to < 9 Years.

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

Intervention / Treatment
-----------------
* Biological: CSL425
* Biological: CSL425


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female aged >= 6 months to < 9 years at the time of the first study vaccination. For children < 3 years of age at the time of first vaccination, born at or after 36 weeks of gestation. 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
-----------------
Minimum Age: 6 Months
Maximum Age: 8 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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 hemagglutinin 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-free<br>|
| Experimental: CSL425 (30 mcg)<br>30 mcg of hemagglutinin 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-free<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemagglutination Inhibition (HI) Antibody Titre Seroconversion Rate After the First Vaccination | HI antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination HI antibody titre of 1:40 or more; or participants with a pre-vaccination HI titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre. | Before and 21 days after the first vaccination | 
| HI Antibody Titre Seroconversion Rate After the Second Vaccination | HI antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination HI antibody titre of 1:40 or more; or participants with a pre-vaccination HI titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre. | Before and 21 days after the second vaccination | 
| Geometric Mean Fold Increase (GMFI) in the HI Antibody Titre After the First Vaccination | GMFI in HI antibody titre was defined as the geometric mean of the fold increase in the post-vaccination antibody titre over the pre-vaccination antibody titre. | Before and 21 days after the first vaccination | 
| GMFI in the HI Antibody Titre After the Second Vaccination | GMFI in HI antibody titre was defined as the geometric mean of the fold increase in the post-vaccination antibody titre over the pre-vaccination antibody titre. | Before and 21 days after the second vaccination | 
| Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More After the First Vaccination |  | 21 days after the first vaccination | 
| Percentage of Participants Achieving a HI 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 |
| --- | --- | --- |
| Frequency and Intensity of Solicited Adverse Events (AEs) After the First or Second Vaccination | Solicited AEs included AEs that were specifically sought for. Grade 3 solicited AE definitions: Cried when limb was moved/spontaneously painful (Cohort A) or prevented normal daily activities (Cohort B) for injection site pain; Size > 100 mm for injection site redness and induration/swelling; Temperature > 103.1°F (39.5°C) for fevers; Prevented normal daily activities or required medical intervention for all other systemic AEs. | During the 7 days after each vaccination | 
| Duration of Solicited AEs After the First Vaccination | Solicited AEs included AEs that were specifically sought for. | During the 7 days after the first vaccination and up to Day 20 after the first vaccination if AE is ongoing at Day 7. | 
| Duration of Solicited AEs After the Second Vaccination | Solicited AEs included AEs that were specifically sought for. | During the 7 days after the second vaccination and up to Day 20 after the second vaccination if AE was 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 Adverse Events After the First or Second Vaccination | Unsolicited AEs included AEs other than those specifically sought for. Grade 1 unsolicited AE definition: Easily tolerated and did not interfere with normal daily activities. Grade 2 unsolicited AE definition: Some interference with normal daily activities. Grade 3 unsolicited AE definition: Prevented normal daily activities. | During the 21 days after each vaccination; up to 180 days after the last vaccination for SAEs, AESIs, and NOCIs |