Safety and Protectiveness of the Seasonal Influenza Vaccine for 2010-2011

Study Overview
=================
Brief Summary
-----------------
The seasonal influenza vaccination program for 2010-2011 will be the first to follow the H1N1 pandemic of 2009. Many Canadians either had the H1N1 infection or the adjuvanted H1N1 vaccine. Both H1N1 infection and adjuvanted vaccine produced strong immune responses which could last for some time. The seasonal influenza vaccine for this fall will be a normal product once again, without adjuvant. It will contain 3 strains of killed, split-apart viruses that might circulate this winter, including the H1N1 pandemic strain. It is theoretically possible that giving the H1N1-containing seasonal vaccine to people who still have some immunity to H1N1 virus could result in more frequent side-effects. However, there is no good evidence that pre-existing immunity to a strain in the vaccine does increase side-effects. In short, there could be nothing out of the ordinary this fall but it would be prudent to check this before public flu vaccination programs begin.

Detailed Description
-----------------
This study will assess the safety of seasonal influenza vaccination in people who had the adjuvanted H1N1 vaccine last year. It will also measure residual immunity to the H1N1 virus and immune responses to the seasonal vaccine. It will be carried out before the new vaccine is released for general use so that we have an accurate picture of vaccine safety and responses for other Canadians. A total of 320 adults (64 at each site) 20 to 59 years old, are being asked to participate in this study. A research nurse will conduct a telephone screening with potential participants to determine if they are eligible for the study. Volunteers must have had adjuvanted H1N1 vaccine before January 31, 2010. The study involves 2 vaccination visits 10 days part. At one visit seasonal vaccine will be given and at the other a placebo vaccine will be given. Which vaccine is given first will be determined by random chance, the details of which will not be released until study end. After each vaccination, there will be contacts 1 and 7 days later for a description of any symptoms experienced. A blood sample will be requested at the first and last visits (visit 3) to measure immune responses to the seasonal vaccine. The study will take 21-38 days to complete, depending upon the vaccination sequence and availability. Total time required to take part is about 2.5 hours. The 3 study visits will occur at a clinic in Vancouver, Calgary, Ottawa, Montreal or Quebec City. Each subject will be asked to keep daily notes of any changes at the injection site (pain, redness, swelling) and any general symptoms (such as headache, tiredness, body aches), including your oral temperature, for 7 days after each vaccination. Major health changes will be assessed for 21 days post 'vaccination' A special Safety Board will review the results of the first vaccinations and advise whether it is reasonable to continue the study or not.

Official Title
-----------------
A Randomized, Blinded, Placebo-controlled, Cross-over Study of the Safety and Immunogenicity of Trivalent, Inactivated Influenza Vaccine for 2010-2011

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

Intervention / Treatment
-----------------
* Biological: Fluviral 2010/11 Tri-valent Seasonal Influenza vaccine
* Biological: Fluviral 2010/11 Tri-valent Seasonal Influenza vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent Can and will comply with the requirements of the protocol Age 20-59 years at Visit 1 Receipt of one dose of Arepanrix (adjuvanted H1N12009 vaccine, GSK) in 2009 documented by written record or attested by a confident personal recollection (window for vaccination will be 1 October 2009 to January 31, 2010). Exclusion Criteria: Systemic hypersensitivity to hens' eggs or to any other Fluviral S/F vaccine component such as thimerosal History of a life-threatening reaction to any influenza vaccine Receipt of non-study TIV for the 2010-2011 season Receipt of any live vaccine within 4 weeks or inactivated vaccine within one week of study entry or planned administration of any non-study vaccines during the study period Thrombocytopenia or any bleeding disorder that contraindicates IM injection or blood collection Pregnancy, at any stage of gestation Receipt of blood or any blood-derived products within 3 months prior to Visit 1 Chronic illness at a stage that could interfere with trial participation (stable health conditions are acceptable, such as diabetes, lung disease, heart conditions etc) History of Guillain-Barre syndrome Immune compromise as a result of illness or immunosuppressive medication Participation in any other research study involving a non-approved drug or medical device Any other condition that may interfere with ability to comply with trial procedures, including abuse of alcohol, drug addiction or imposed confinement Current febrile illness or oral temperature of ≥ 38.0 °C

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 59 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group 1<br>FLuviral 2010/11Tri-valent Seasonal Influenza Vaccine (TIV)1st; saline placebo 10 days later | Biological: Fluviral 2010/11 Tri-valent Seasonal Influenza vaccine<br>* Vaccination of .05mL of Fluviral vaccine will be injected once at either visit 1 or 2 depending upon randomization in the deltoid muscle of the non-dominant arm<br>|
| Placebo Comparator: Group 2<br>Saline placebo 1st; Fluviral 2010/11 Tri-valent Seasonal Influenza Vaccine (TIV)10 days later | Biological: Fluviral 2010/11 Tri-valent Seasonal Influenza vaccine<br>* Vaccination of .05mL of Fluviral vaccine will be injected once at either visit 1 or 2 depending upon randomization in the deltoid muscle of the non-dominant arm<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety of 2010-2011 seasonal trivalent vaccine (TIV) | To evaluate the safety of 2010-2011 seasonal trivalent vaccine (TIV) in a convenience sample of adults being re-vaccinated with H1N12009 antigen, as soon as vaccine becomes available so as to inform subsequent use of the vaccine in public programs. | 12 weeks | 
| To measure immune responses to each component of TIV | To measure immune responses to each component of TIV prior to and following seasonal vaccination to assess the immunogenicity of the new TIV vaccine. | 12 weeks | 
| To observe the persistence of anti-HAI responses to H1N12009 | To observe the persistence of anti-HAI responses to H1N12009 in a subset of subjects previously studied after vaccination with adjuvanted pandemic vaccine in late 2009 and to compare their peak responses to H1N12009 after the pandemic and TIV vaccinations. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine-attributable rates of the observed adverse events | The secondary safety outcomes will be the vaccine-attributable rates of the observed adverse events, both local and general, | 12 weeks | 
| Immunogenicity analysis performed on the according-to-protocol (ATP) cohort | The secondary immunogenicity outcome will be the immunogenicity analysis performed on the according-to-protocol (ATP) cohort, comprising subjects with complete data for the principal immunogenicity endpoints and no major protocol deviations. The key immunogenicity outcome will be whether the HAI antibody responses to each vaccine strain meet the EMEA/CHMP criteria (3) for seasonal TIV vaccine responses in adults <60 years of age. | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vaccine, Seasonal Influenza vaccine, Influenza vaccine, Vaccine safety, Vaccine immunogenicity, Fluviral 2010/11