Immunogenicity and Safety Study to Assess Influenza Vaccine Formulated With Haemagglutinin (HA) Antigen From Two Suppliers

Study Overview
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Brief Summary
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The purpose of this study is to assess the humoral immune response and safety of the parenteral formulation of the 2010/2011-season virosomal subunit influenza vaccine Inflexal V using two different HA antigen suppliers (AdImmune and CSL), in groups of young and elderly adults, using the EMA (European Medicines Agency) regulation as a guideline.

Detailed Description
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The objectives of this study are to evaluate the humoral immunogenicity and safety of the parenteral formulation of the 2010/2011-season influenza vaccine, Inflexal V, using HA antigen obtained from 2 different production facilities, and to compare the immunogenicity of both formulations to pre-defined EMA criteria for the annual relicensing of seasonal influenza vaccines. The evaluation will be done in young adults and elderly.

Official Title
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Randomized, Parallel-group, Double-blind Multi-center Phase III Study to Assess the Immunogenicity and Safety of the 2010/2011-season Influenza Vaccine Formulated With Haemagglutinin (HA) Antigen From Two Suppliers, in Elderly and Young Adults

Conditions
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Influenza

Intervention / Treatment
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* Biological: Inflexal V influenza vaccine (CSL HA Antigen) 2010
* Biological: Inflexal V influenza vaccine (AdImmune HA antigen) 2010/2011


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy female and male adults Aged ≥18 years on Day 1 Written informed consent Exclusion Criteria: Acute exacerbation of bronchopulmonary infection (cough, sputum, lung findings) or other acute disease Acute febrile illness (≥38.0 °C) Prior vaccination with an influenza vaccine (including the H1N1 pandemic swine flu vaccine) in the past 330 days Known hypersensitivity to any vaccine component Previous history of a serious adverse reaction to influenza vaccine History of egg protein allergy or severe atopy Known blood coagulation disorder Chronic (longer than 14 days) administration of immunosuppressants or other immune-modifying drugs within 6 months before the first dose of the study vaccine, incl. oral corticosteroids in dosages of ≥0.5 mg/kg/d prednisolone or equivalent (inhaled or topical steroids are allowed) Known immunodeficiency (incl. leukemia, cancer, HIV seropositivity) Investigational medicinal product received in the past 3 months (90 days) Treatment with immunoglobulins or blood transfusion(s) received in the past 3 months (90 days) Pregnancy or lactation Participation in another clinical trial Employee at the investigational site, or spouse and children of the investigator, or relative living in the same household as the investigator and/or are dependent on the investigator Suspected non-compliance

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Subjects ≥18 to ≤60 Years - CSL HA Antigen<br>Inflexal V influenza vaccine (CSL HA Antigen) 2010 Group A will be vaccinated with Inflexal V influenza vaccine (surface antigen, inactivated, virosome, using CSL HA Antigen) 2010/2011 containing per 0.5 mL i.m. dose: 15 μg HA antigen of A/California/7/2009 (H1N1)-like virus; 15 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus; 15 μg HA antigen of B/Brisbane/60/2008-like virus | Biological: Inflexal V influenza vaccine (CSL HA Antigen) 2010<br>* Inflexal V influenza vaccine (surface antigen, inactivated, virosome, using CSL HA Antigen) 2010/2011, with intramuscular administration, containing per 0.5 mL dose: 15 μg HA antigen of A/California/7/2009 (H1N1)-like virus; 15 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus; 15 μg HA antigen of B/Brisbane/60/2008-like virus<br>|
| Active Comparator: Subjects >60 Years - CSL HA Antigen<br>Inflexal V influenza vaccine (CSL HA Antigen) 2010 Group B will be vaccinated with Inflexal V influenza vaccine (surface antigen, inactivated, virosome, using CSL HA Antigen) 2010/2011 containing per 0.5 mL i.m. dose: 15 μg HA antigen of A/California/7/2009 (H1N1)-like virus; 15 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus; 15 μg HA antigen of B/Brisbane/60/2008-like virus | Biological: Inflexal V influenza vaccine (CSL HA Antigen) 2010<br>* Inflexal V influenza vaccine (surface antigen, inactivated, virosome, using CSL HA Antigen) 2010/2011, with intramuscular administration, containing per 0.5 mL dose: 15 μg HA antigen of A/California/7/2009 (H1N1)-like virus; 15 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus; 15 μg HA antigen of B/Brisbane/60/2008-like virus<br>|
| Experimental: Subjects ≥18 to ≤60 Years - AdImmune HA Antigen<br>Inflexal V influenza vaccine (AdImmune HA Antigen) 2010/2011 Group C will be vaccinated with Inflexal V influenza vaccine (surface antigen, inactivated, virosome, using AdImmune HA antigen) 2010/2011 containing per 0.5 mL i.m.dose: 15 μg HA antigen of A/California/7/2009 (H1N1)-like virus; 15 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus; 15 μg HA antigen of B/Brisbane/60/2008-like virus | Biological: Inflexal V influenza vaccine (AdImmune HA antigen) 2010/2011<br>* Inflexal V influenza vaccine (surface antigen, inactivated, virosome, using AdImmune HA antigen) 2010/2011 with intramuscular administration, containing per 0.5 mL dose: 15 μg HA antigen of A/California/7/2009 (H1N1)-like virus; 15 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus; 15 μg HA antigen of B/Brisbane/60/2008-like virus<br>|
| Experimental: Subjects >60 Years - AdImmune HA Antigen<br>Inflexal V influenza vaccine (AdImmune HA Antigen) 2010/2011 Group D will be vaccinated with Inflexal V influenza vaccine (surface antigen, inactivated, virosome, using AdImmune HA antigen) 2010/2011 containing per 0.5 mL i.m.dose: 15 μg HA antigen of A/California/7/2009 (H1N1)-like virus; 15 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus; 15 μg HA antigen of B/Brisbane/60/2008-like virus | Biological: Inflexal V influenza vaccine (AdImmune HA antigen) 2010/2011<br>* Inflexal V influenza vaccine (surface antigen, inactivated, virosome, using AdImmune HA antigen) 2010/2011 with intramuscular administration, containing per 0.5 mL dose: 15 μg HA antigen of A/California/7/2009 (H1N1)-like virus; 15 μg HA antigen of A/Perth/16/2009 (H3N2)-like virus; 15 μg HA antigen of B/Brisbane/60/2008-like virus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity - Geometric Mean Titer Fold Increase From Baseline | The primary endpoints were the immunogenicity parameters for HA assessed via hemagglutinin inhibition method (HI). These parameters were analyzed according to the EMA Note for guidance on harmonisation of requirements for influenza vaccines, 1997 and they were the following: 1. Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40, 2. Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40, 3. GMT of HI antibodies and fold-increase in GMT | 3 weeks after vaccination (Day 22 ± 2 days) | 
| Immunogenicity - Seroprotection Rate | The primary endpoints were the immunogenicity parameters for HA assessed via hemagglutinin inhibition method (HI). These parameters were analyzed according to the EMA Note for guidance on harmonisation of requirements for influenza vaccines, 1997 and they were the following: 1. Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40, 2. Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40, 3. GMT of HI antibodies and fold-increase in GMT | 3 weeks after vaccination (Day 22 ± 2 days) | 
| Immunogenicity - Seroconversion Rate | The primary endpoints were the immunogenicity parameters for HA assessed via hemagglutinin inhibition method (HI). These parameters were analyzed according to the EMA Note for guidance on harmonisation of requirements for influenza vaccines, 1997 and they were the following: 1. Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40, 2. Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40, 3. GMT of HI antibodies and fold-increase in GMT | 3 weeks after vaccination (Day 22 ± 2 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Local and Systemic Adverse Events | Solicited local and systemic AEs, Unsolicited AEs, Tolerability and acceptability Unsolicited AEs were collected from baseline (Day 1) to 3 weeks after vaccination (Day 22 ± 2 days). Solicited local and systemic AEs were collected by subjects diary from Day 1 (day of vaccination) to Day 4 | Baseline (Day 1) and 3 weeks after vaccination (Day 22 ± 2 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Virus, Vaccination, Immunisation