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Comparison of 4 Influenza Vaccines in Seniors (PCIRNRT09)

Primary Purpose

Influenza Vaccine

Status
Completed
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Agriflu
Fluad
Intanza
Vaxigrip
Sponsored by
University of British Columbia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Influenza Vaccine focused on measuring Vaccine, Influenza vaccine, Adjuvanted Influenza vaccine, Intradermal Influenza vaccine, Seniors, Acceptability of vaccines, Influenza

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Written informed consent provided by the subject, who can be male or female
  • Subjects who the investigator believes can and will comply with the requirements of the protocol (i.e. return for follow-up visits, record safety observations and able to converse with study personnel including by personal telephone)
  • Age 65 years or older at Visit 1
  • Generally good health (stable chronic conditions acceptable), living independently or with minimal assistance (Clinical Frailty score 1-5) (33) and able to attend clinic appointments
  • Receipt of at least one dose of TIV within the previous 2 influenza seasons, documented by written record or attested by a confident personal recollection. This refers to the trivalent seasonal vaccine, not the H1N12009 pandemic vaccine.

Exclusion Criteria:

  • receipt of non-study influenza vaccine for 2011-12
  • receipt of any live vaccine within 4 weeks or inactivated vaccine within one week of Visit 1 or planned administration of any non-study vaccines between Visits 1 and 2
  • systemic hypersensitivity to influenza vaccine, hen's eggs or other vaccine constituent (eg neomycin sulphate, kanamycin, formalin)
  • severe reaction to any previous influenza vaccine or vaccine component
  • bleeding disorder, including anticoagulant therapy or thrombocytopenia, that contraindicates IM injection or blood collection (does not include daily low-dose ASA).
  • incapacity to provide fully informed consent or be attentive to follow-up observations, resulting from cognitive impairment, abuse of alcohol, drug addiction
  • lack of telephone access, inadequate fluency in English (or French in applicable jurisdictions), uncertain availability during the 3 week study participation period or for the 6 month follow-up visit
  • immune compromise resulting from disease or immunosuppressive systemic medication use within 3 months of V1
  • receipt of blood or blood product within 3 months of V1
  • unstable medical condition, as indicated by a requirement for hospitalization or a substantial medication change to stabilize said condition within previous 3 months
  • Clinical Frailty score of 6-7 (moderately frail or severely frail)
  • history of Guillain-Barré syndrome

Sites / Locations

  • University of British Columbia, VITALiTY Research Center
  • University of Manitoba, Department of Medicine
  • Canadian Centre for Vaccinology Dalhousie University
  • McMaster University
  • The Ottawa Hospital Research Institute, University of Ottawa
  • University of Toronto, Mt Sinai Hospital
  • McGill University Health Center - Vaccine Study Center
  • Unité de Recherche en Santé Publique (CHUQ),

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Trivalent Influenza vaccine subunit

Adjuvanted Tri-valent Influenza Vaccine

Intradermal Tri-valent Influenza vaccine

Trivalent Split-virion Influenza vaccine

Arm Description

The seasonal vaccine (Agriflu, Novartis) contains egg-derived, inactivated and detergent split versions of the 3 influenza strains (tri-valent). It is given into the muscle of the upper arm at a dose of 0.5 mL.

The adjuvanted vaccine (Fluad, Novartis) is made with an immune-stimulator (MF59) that contains squalene oil microdroplets and two surfactants, Tween 80 and Span 65. It is given into the muscle of the upper arm at a dose of 0.5 mL.

(Intanza 15ug, Sanofi Pasteur) is an inactivated, split-virion influenza vaccine. Strains are grown in fertilized hen's eggs, inactivated with formalin and split using Triton X-100 detergent, as for TIV. The syringe is attached to a micro-needle injection system (Beckton Dickinson) that limits the depth of injection to just under the skin. It is given into the skin over the upper arm at a dose of 0.1 mL.

Vaxigrip, Sanofi Pasteur is an inactivated, split-virion Influenza vaccine. The 3 influenza strains are grown on fertilized eggs, concentrated, purified in a sugar-like solution, detergent split, and inactivated by formaldehyde, then diluted in phosphate buffered salt solution. A dose of 0.5 mL is given into the muscle of the arm.

Outcomes

Primary Outcome Measures

HAI response
The primary outcome measures will be the 3-week post-vaccination immune (HAI) responses to the 3 vaccine strains present in each product, assessed by the EMEA/CHMP criteria for evaluation of immune responses to influenza vaccines in persons >60 years of age.

Secondary Outcome Measures

Seroprotection rates using microneutralization titres and cytokine testing
As secondary immunologic outcomes seroprotection rates will be compared between the products using a higher titer (≥160) as threshold. Microneutralization titers will be compared among products at the 3 sampling points, using sera from 100 subjects per group. Cross-protection afforded by each vaccine against drift variants of H3N2, H1N1 and B viruses will be assessed using serum panels selected from 50 subjects in each group. Cellular immune responses elicited will be compared in subgroups of 30 subjects per vaccine in the CMI subjset.
Safety and Acceptability
Safety and acceptability of the vaccines will also be examined and compared as the safety outcomes. The primary outcome measurements will be the rates of local adverse events (pain, redness, swelling, itchiness) as rates of general adverse events are not expected to differ substantially among the products.

Full Information

First Posted
June 6, 2011
Last Updated
April 14, 2015
Sponsor
University of British Columbia
Collaborators
PHAC/CIHR Influenza Research Network
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1. Study Identification

Unique Protocol Identification Number
NCT01368796
Brief Title
Comparison of 4 Influenza Vaccines in Seniors
Acronym
PCIRNRT09
Official Title
Controlled Comparison in Canadian Seniors of Seasonal Influenza Vaccines for 2011-2012
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
May 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of British Columbia
Collaborators
PHAC/CIHR Influenza Research Network

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Based on information from several years of looking at Influenza vaccination doctors know that: Older adults suffer the worst illness and most deaths caused by Influenza illness of all age groups. Older adults do not seem to get as good a level of protection as younger adults after getting the usual seasonal Influenza vaccine. Because of this information doctors wonder if one of the new seasonal Influenza vaccines is more effective or more acceptable. This study has been designed to answer some of these questions. On this study doctors will compare 2 new vaccines against the usual seasonal influenza vaccine for protectiveness using several different testing methods (including the usual tests) and for acceptability.
Detailed Description
This study is prospective, multicenter, randomized, evaluator-blinded, controlled, parallel group study of 3 licensed seasonal influenza vaccine products conducted in seniors, with a 4th vaccine included in a substudy of cellular immune responses. Ambulatory adults 65+ years of age, in good health or with stable health conditions, given TIV within the past 2 years, will be recruited in multiple Canadian centres. Subjects can be dwelling in the community or in centers providing minimal assisted living support. A total of 930 subjects will be enrolled. Subjects will be centrally (electronically) randomized to receive either TIV, IDV or AIV on Day 0. Three blood samples will be collected (1 pre and 2 post vaccination) to measure HAI antibody responses to each virus strain (H1N1, H3N2 and B) in each vaccine, using standardized assays. Randomly selected subsets of sera from each study group will also be tested for neutralizing antibody and for cross-protection against drift variants of H3N2, H1N1 and B viruses. In a subset of subjects in Vancouver, randomization assignments will include TIV2 and extra blood samples will be obtained 0, 21 and 72 days post vaccination for CMI testing. Safety assessments will be conducted on Day 7, Day 21 and Day 180 following vaccination. Acceptability of each product, reflecting the frequency, severity and tolerability of adverse effects, will be assessed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza Vaccine
Keywords
Vaccine, Influenza vaccine, Adjuvanted Influenza vaccine, Intradermal Influenza vaccine, Seniors, Acceptability of vaccines, Influenza

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
953 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Trivalent Influenza vaccine subunit
Arm Type
Active Comparator
Arm Description
The seasonal vaccine (Agriflu, Novartis) contains egg-derived, inactivated and detergent split versions of the 3 influenza strains (tri-valent). It is given into the muscle of the upper arm at a dose of 0.5 mL.
Arm Title
Adjuvanted Tri-valent Influenza Vaccine
Arm Type
Active Comparator
Arm Description
The adjuvanted vaccine (Fluad, Novartis) is made with an immune-stimulator (MF59) that contains squalene oil microdroplets and two surfactants, Tween 80 and Span 65. It is given into the muscle of the upper arm at a dose of 0.5 mL.
Arm Title
Intradermal Tri-valent Influenza vaccine
Arm Type
Active Comparator
Arm Description
(Intanza 15ug, Sanofi Pasteur) is an inactivated, split-virion influenza vaccine. Strains are grown in fertilized hen's eggs, inactivated with formalin and split using Triton X-100 detergent, as for TIV. The syringe is attached to a micro-needle injection system (Beckton Dickinson) that limits the depth of injection to just under the skin. It is given into the skin over the upper arm at a dose of 0.1 mL.
Arm Title
Trivalent Split-virion Influenza vaccine
Arm Type
Active Comparator
Arm Description
Vaxigrip, Sanofi Pasteur is an inactivated, split-virion Influenza vaccine. The 3 influenza strains are grown on fertilized eggs, concentrated, purified in a sugar-like solution, detergent split, and inactivated by formaldehyde, then diluted in phosphate buffered salt solution. A dose of 0.5 mL is given into the muscle of the arm.
Intervention Type
Biological
Intervention Name(s)
Agriflu
Intervention Description
0.5mL dose IM vaccination
Intervention Type
Biological
Intervention Name(s)
Fluad
Intervention Description
0.5mL dose of vaccine given IM
Intervention Type
Biological
Intervention Name(s)
Intanza
Intervention Description
0.5mL dose vaccine given IM
Intervention Type
Biological
Intervention Name(s)
Vaxigrip
Intervention Description
0.5mL dose vaccine given IM
Primary Outcome Measure Information:
Title
HAI response
Description
The primary outcome measures will be the 3-week post-vaccination immune (HAI) responses to the 3 vaccine strains present in each product, assessed by the EMEA/CHMP criteria for evaluation of immune responses to influenza vaccines in persons >60 years of age.
Time Frame
Day 0; Day 21; Day 180
Secondary Outcome Measure Information:
Title
Seroprotection rates using microneutralization titres and cytokine testing
Description
As secondary immunologic outcomes seroprotection rates will be compared between the products using a higher titer (≥160) as threshold. Microneutralization titers will be compared among products at the 3 sampling points, using sera from 100 subjects per group. Cross-protection afforded by each vaccine against drift variants of H3N2, H1N1 and B viruses will be assessed using serum panels selected from 50 subjects in each group. Cellular immune responses elicited will be compared in subgroups of 30 subjects per vaccine in the CMI subjset.
Time Frame
Day 0; Day 21; and Day 70
Title
Safety and Acceptability
Description
Safety and acceptability of the vaccines will also be examined and compared as the safety outcomes. The primary outcome measurements will be the rates of local adverse events (pain, redness, swelling, itchiness) as rates of general adverse events are not expected to differ substantially among the products.
Time Frame
Days 0-6; Day 21; Day 70; and Day 180

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Written informed consent provided by the subject, who can be male or female Subjects who the investigator believes can and will comply with the requirements of the protocol (i.e. return for follow-up visits, record safety observations and able to converse with study personnel including by personal telephone) Age 65 years or older at Visit 1 Generally good health (stable chronic conditions acceptable), living independently or with minimal assistance (Clinical Frailty score 1-5) (33) and able to attend clinic appointments Receipt of at least one dose of TIV within the previous 2 influenza seasons, documented by written record or attested by a confident personal recollection. This refers to the trivalent seasonal vaccine, not the H1N12009 pandemic vaccine. Exclusion Criteria: receipt of non-study influenza vaccine for 2011-12 receipt of any live vaccine within 4 weeks or inactivated vaccine within one week of Visit 1 or planned administration of any non-study vaccines between Visits 1 and 2 systemic hypersensitivity to influenza vaccine, hen's eggs or other vaccine constituent (eg neomycin sulphate, kanamycin, formalin) severe reaction to any previous influenza vaccine or vaccine component bleeding disorder, including anticoagulant therapy or thrombocytopenia, that contraindicates IM injection or blood collection (does not include daily low-dose ASA). incapacity to provide fully informed consent or be attentive to follow-up observations, resulting from cognitive impairment, abuse of alcohol, drug addiction lack of telephone access, inadequate fluency in English (or French in applicable jurisdictions), uncertain availability during the 3 week study participation period or for the 6 month follow-up visit immune compromise resulting from disease or immunosuppressive systemic medication use within 3 months of V1 receipt of blood or blood product within 3 months of V1 unstable medical condition, as indicated by a requirement for hospitalization or a substantial medication change to stabilize said condition within previous 3 months Clinical Frailty score of 6-7 (moderately frail or severely frail) history of Guillain-Barré syndrome
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David W Scheifele, MD
Organizational Affiliation
University of Britich Columbia
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of British Columbia, VITALiTY Research Center
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
University of Manitoba, Department of Medicine
City
Winnipeg
State/Province
Manitoba
Country
Canada
Facility Name
Canadian Centre for Vaccinology Dalhousie University
City
Halifax
State/Province
Nova Scotia
Country
Canada
Facility Name
McMaster University
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
The Ottawa Hospital Research Institute, University of Ottawa
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
University of Toronto, Mt Sinai Hospital
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
McGill University Health Center - Vaccine Study Center
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Unité de Recherche en Santé Publique (CHUQ),
City
Quebec City
State/Province
Quebec
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
22872731
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.
Results Reference
derived

Learn more about this trial

Comparison of 4 Influenza Vaccines in Seniors

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