Clinical trial NCT01140009: Safety and Protectiveness of the Seasonal Influenza Vaccine for 2010-2011
Official title: A Randomized, Blinded, Placebo-controlled, Cross-over Study of the Safety and Immunogenicity of Trivalent, Inactivated Influenza Vaccine for 2010-2011
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Keywords: Vaccine
Seasonal Influenza vaccine
Influenza vaccine
Vaccine safety
Vaccine immunogenicity
Fluviral 2010/11
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: GlaxoSmithKline
First posted: 2010-06-09
Enrollment: 324
Sex: ALL
Minimum age (years): 20
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: To evaluate the safety of 2010-2011 seasonal trivalent vaccine (TIV)
timeFrame: 12 weeks
measure: To measure immune responses to each component of TIV
timeFrame: 12 weeks
measure: To observe the persistence of anti-HAI responses to H1N12009
timeFrame: 12 weeks
Secondary outcomes:
measure: Vaccine-attributable rates of the observed adverse events
timeFrame: 12 weeks
measure: Immunogenicity analysis performed on the according-to-protocol (ATP) cohort
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: ACHIEVE Research, Alberta Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Vaccine Evaluation Center
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital Research Institute
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre - Vaccine Study Centre
state: Quebec
city: Quebec City
country: Canada
facility: Unité de Recherche en Santé Publique
state: Quebec
Study officials:
affiliation: University of British Columbia
name: David Scheifele, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Simon Dobson, Dr.
role: STUDY_DIRECTOR
affiliation: University of British Columbia
name: Laura Sauve, Dr.
role: STUDY_DIRECTOR
affiliation: University of British Columbia
name: Tobias Kollmann, Dr.
role: STUDY_DIRECTOR
affiliation: University of British Columbia
name: Keswadee Lapphra, Dr.
role: STUDY_DIRECTOR
affiliation: McGill University Health Centre - Vaccine Study Centre
name: Brian Ward, Dr.
role: STUDY_DIRECTOR
affiliation: Unité de Recherche en Santé Publique (CHUQ)
name: Marc Dionne, Dr.
role: STUDY_DIRECTOR
affiliation: Unité de Recherche en Santé Publique (CHUQ)
name: Vladimir Gilca, Dr.
role: STUDY_DIRECTOR
affiliation: Unité de Recherche en Santé Publique (CHUQ)
name: Gaston DeSerres, Dr.
role: STUDY_DIRECTOR
affiliation: The Ottawa Hospital Research Institute, University of Ottawa
name: Curtis Cooper, Dr.
role: STUDY_DIRECTOR
affiliation: ACHIEVE Research, Alberta Children's Hospital, University of Calgary and Alberta Health Services
name: Otto Vanderkooi, Dr.
role: STUDY_DIRECTOR
affiliation: ACHIEVE Research, Alberta Children's Hospital, University of Calgary and Alberta Health Services
name: James Kellner, Dr.
role: STUDY_DIRECTOR
affiliation: ACHIEVE Research, Alberta Children's Hospital, University of Calgary and Alberta Health Services
name: Judy MacDonald, Dr.
role: STUDY_DIRECTOR
References:
citation: Skowronski DM, Janjua NZ, De Serres G, Purych D, Gilca V, Scheifele DW, Dionne M, Sabaiduc S, Gardy JL, Li G, Bastien N, Petric M, Boivin G, Li Y. Cross-reactive and vaccine-induced antibody to an emerging swine-origin variant of influenza A virus subtype H3N2 (H3N2v). J Infect Dis. 2012 Dec 15;206(12):1852-61. doi: 10.1093/infdis/jis500. Epub 2012 Aug 7.