Safety, and Immunogenicity of Two Influenza Vaccines in Healthy Subjects 3 to 64 Years Old

Study Overview
=================
Brief Summary
-----------------
This protocol is designed to evaluate safety, clinical tolerability and immunogenicity of the 2007 southern hemisphere formulation of a Novartis conventional influenza vaccine licensed in the EU and many other worldwide countries, according to the US FDA Draft Guidance for Industry Clinical data needed to support the licensure of trivalent inactivated influenza vaccine, issued in March 2006, and to evaluate safety, clinical tolerability and immunogenicity of the 2007 southern hemisphere formulation of a Novartis conventional influenza vaccine already licensed in US. The purpose of the control arm is primarily to provide a comparative assessment for safety, not immunogenicity or effectiveness.

Official Title
-----------------
A Phase III, Observer-Blind, Randomized, Controlled, Multicenter Study to Evaluate Safety, Tolerability, and Immunogenicity of Two Trivalent Subunit Inactivated Influenza Vaccines in Healthy Children Aged 3 to 8 Years, in Healthy Children/Adolescents Aged 9 to 17 Years,and in Healthy Adults Aged 18 to 64 Years

Conditions
-----------------
Influenza

Intervention / Treatment
-----------------
* Biological: Influenza virus vaccine
* Biological: Comparator influenza vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy subjects 3 to 64 years of age Exclusion Criteria: Receipt of other investigational products within 3 months or other vacine within 1 month; Allergy to eggs, egg products, or any other vaccine component; Laboratory confirmed influenza disease within 6 months; Have previously received an influenza vaccination (3 to 8 years only);

Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 64 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Influenza virus vaccine<br> | Biological: Influenza virus vaccine<br>* Two intramuscular injections of the investigational influenza virus vaccine administered 4 weeks part to group 3 to 8 years of age while one injection was administered to groups 9 to 17 years of age and 18 to 64 years of age.<br>|
| Active Comparator: Comparator influenza vaccine<br> | Biological: Comparator influenza vaccine<br>* Two intramuscular injections were administered 4 weeks apart to group 3 to 8 years of age while one injection was administered to groups 9 to 17 years of age and 18 to 64 years of age.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Seroprotection, in Healthy Adults 18 to 64 Years of Age | To evaluate immunogenicity, measured by seroprotection (percentage of subjects achieving a hemagglutination inhibition [HI] titer ≥40) after one injection of the investigational influenza virus vaccine, administered to healthy adults 18 to 64 years of age. The CBER Guidance states that the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroprotection meet or exceed 70%. | 21 days after vaccination | 
| Percentage of Subjects Achieving a Seroconversion Rate, in Adults 18 to 64 Years of Age | Seroconversion rate is defined as percentage of subjects achieving seroconversion (defined as negative pre-vaccination serum [HI<10]/ post-vaccination HI titer ≥40) or significant increase defined as at least a 4-fold increase). According to the CBER Guidance, the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconverion/significant increase meet or exceed 40%. | 21 days after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Solicited Local and Systemic Symptoms in Adults 18 to 64 Years of Age | Solicited local and systemic reactions were assessed after vaccination in adults 18 to 64 years of age. | 7 days after vaccination | 
| Percentage of Subjects With Seroprotection, in Healthy Children/Adolescents 9 to 17 Years of Age | To descriptively evaluate immunogenicity, measured by seroprotection rate (percentage of subjects achieving a hemagglutination inhibition [HI] titer ≥40) after one injection of investigational influenza virus vaccine, administered to healthy children/adolescents 9 to 17 years of age. | 21 days after vaccination | 
| Percentage of Subjects Achieving Seroconversion Rate, in Healthy Children/Adolescents 9 to 17 Years of Age | Seroconversion rate is defined as percentage of subjects achieving seroconversion (defined as negative pre-vaccination serum [HI<10]/ post-vaccination HI titer ≥40) or significant increase (defined as at least a 4-fold increase) after one injection of the investigational influenza virus vaccine, administered to healthy children/adolescents 9 to 17 years of age. | 21 days after vaccination | 
| Geometric Mean Titers (GMTs), in Healthy Children/Adolescents 9 to 17 Years of Age | To evaluate immunogenicity measured by GMTs after one injection of investigational influenza virus vaccine, administered to healthy children/adolescents 9 to 17 years of age. | 21 days after vaccination | 
| Number of Subjects Reporting Solicited Local and Systemic Symptoms in Children/Adolescents 9 to 17 Years of Age | Solicited local and systemic reactions were assessed after vaccination in children/adolescents 9 to 17 years of age. | 7 days after vaccination | 
| Percentage of Subjects With Seroprotection, in Healthy Children 3 to 8 Years of Age | To descriptively evaluate immunogenicity, measured by seroprotection rate (percentage of subjects achieving a hemagglutination inhibition [HI] titer ≥40) after two injections of the investigational influenza virus vaccine, in healthy children 3 to 8 years of age. | 50 days after last vaccination | 
| Percentage of Subjects Achieving Seroconversion Rate, in Healthy Children 3 to 8 Years of Age | Seroconversion rate is defined as percentage of subjects achieving seroconversion (defined as negative pre-vaccination serum [HI<10]/ post-vaccination HI titer ≥40) or significant increase (defined as at least a 4-fold increase) after two injections of the investigational influenza virus vaccine, in healthy children 3 to 8 years of age. | 50 days after last vaccination | 
| Geometric Mean Titers (GMTs), in Healthy Children 3 to 8 Years of Age | To evaluate immunogenicity measured by GMTs after two injections of the investigational influenza virus vaccine, in healthy children 3 to 8 years of age. | 50 days after last vaccination | 
| Number or Subjects Reporting Solicited Local and Systemic Symptoms, in Healthy Children 3 to 8 Years of Age. | Solicited local and systemic reactions were assessed after each vaccination, in healthy children 3 to 8 years of age. | 7 days after each vaccination | 
| Geometric Mean Titers (GMTs), in Healthy Adults 18 to 64 Years of Age | Immunogenicity measured by GMTs after one injection of the investigational influenza virus vaccine, in healthy adults 18 to 64 years of age. | 21 days after vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Influenza, Egg-Derived, Healthy Children, Healthy Adolescents, Healthy Adults, Safety, Immunogenicity, Trivalent, Inactivated, Vaccination