A Randomized Study to Compare the Safety and Immunogenicity of Fluviral® Made With New Versus Aged Bulk

Study Overview
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Brief Summary
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Vaccination is currently the most effective means of controlling influenza and preventing its complications and mortality in persons at risk. Once a year, a meeting of World Health Organization (WHO) experts takes place, leading to a recommendation on the influenza A and B strains that should be used for the production of vaccine for the coming influenza season. For the strains which do not change from the previous year, the vaccine can be formulated from the old mono bulk from the previous year. Bulks as old as 12 months may be blended to make trivalent inactivated vaccine (TIV) under the current Canadian and US licenses. This study is conducted to evaluate safety and immunogenicity of Fluviral vaccines made with the aged bulk material compared with the new bulk material. This protocol posting has been updated in order to comply with the FDA Amendment Act, Sept 2007.

Official Title
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Observer-blind, Post-Marketing Study to Compare the Safety and Immunogenicity of Fluviral® Trivalent Split Virion Influenza Vaccine (2007-2008 Season) Made With New vs. Aged Bulk Material, in Adults Ranging in Age From 18 to 60 Years

Conditions
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Influenza Vaccines

Intervention / Treatment
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* Biological: Fluviral


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes can and will comply with the requirements of the protocol should be enrolled in the study. Male and female adults, 18 to 60 years. Written informed consent obtained from the subject. If the subject is female, she must be of non-childbearing potential or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for the duration of the study. Exclusion Criteria: Acute disease at the time of enrollment. Any confirmed or suspected immunosuppressive condition Presence of blood dyscrasias, including hemaglobinopathies and myelo- or lymphoproliferative disorder. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. A history of any demyelinating disease including Guillain-Barré syndrome. Presence of an active neurological disorder. Any significant disorder of coagulation that increases the risk of intramuscular injections or treatment with coumadin derivatives or heparin. Receipt of an influenza vaccine within 6 months prior to study enrollment. Administration of any vaccines within 30 days prior to study enrollment or during the study period. Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the vaccination or planned use during the study period. Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the study vaccine or planned during the study. Any known or suspected allergy to any constituent of Fluviral and/or a history of anaphylactic type reaction to consumption of eggs, and/or reactions to products containing mercury. A history of severe adverse reaction to a previous influenza vaccination. Lactating/nursing female. Any condition which, in the opinion of the investigator, prevents the subject from participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Old Bulk<br>This group receives a full dose of Fluviral made from aged bulk material | Biological: Fluviral<br>* One dose, Intramuscular injection<br>|
| Active Comparator: New Bulk<br>This group receives a full dose of Fluviral made from new material | Biological: Fluviral<br>* One dose, Intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of Anti-H3 and B Strains | GMTs for H1 strain is addressed as a secondary endpoint | At Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of the H1 Strain and the GMT of the H3 and B Strains | The table contains GMTs of the H1 strains at Day 0 & 21 and of the H3 and B strains at Day 0 (values at Day 21 for H3 and B strains were primary outcome measures) | At Days 0 and 21 | 
| Number of Participants Who Seroconverted. | The table shows the number of participants who have either a pre-vaccination titer < 1:10 and a post-vaccination titer >= 1:40 or a prevaccination titer >= 1:10 and at least a 4-fold increase in post-vaccination titer, at Day 21. | At Day 21. | 
| Number of Seroprotected Participants. | The table presents the number of participants with a serum haemagglutination inhibition (HI) titer >= 1:40 that usually is accepted as indicating protection. | At Days 0 and 21 | 
| Seroconversion Factors Defined as the Fold Increase in Serum HI GMTs Post-vaccination for Influenza Antigen H1N1 | Seroconversion factors are defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0, at Day 21. This table presents the SCF for the H1 strain. The SCF for the other strains are addressed in the next table. | At Day 21 compared to Day 0 | 
| The Fold Increase in Anti-HI GMTs for Influenza Antigens H3 and B | The fold increase in anti-HI GMTs for influenza antigen H1 is presented in the previous table. The fold increase corresponds to the Unit of Measure Factor. | At Day 21 compared to Day 0 | 
| Number of Participants Reporting Solicited Local Symptoms | Solicited local symptoms assessed include pain, redness and swelling. | During the 4-day follow up period following vaccination. | 
| Number of Participants Reporting Solicited General Symptoms | Solicited general symptoms assessed include bronchospasm, chills, cough, fatigue, fever, headache, joint pain at other location, muscle aches, red eyes, sore throat, and swelling of the face | During the 4-day period following each vaccination. | 
| Number of Participants Reporting Unsolicited Adverse Events (AE). | An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | During the 21-day period following each vaccination. | 
| Number of Participants Reporting Serious Adverse Events (SAE) | An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. | Within 21 days after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza