Clinical trial NCT03330132: Immunogenicity of Alternative Annual Influenza Vaccination Strategies in Older Adults in Hong Kong
Official title: Immunogenicity of Alternative Annual Influenza Vaccination Strategies in Older Adults in Hong Kong - a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Influenza, Human
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
First posted: 2017-11-06
Enrollment: 1861
Sex: ALL
Minimum age (years): 65
Maximum age (years): 82
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Annual vaccination with standard influenza vaccine or enhanced influenza vaccine, including some combination strategies (alternating each year) and some strategies with the same vaccine administered each year
Primary purpose: PREVENTION

Brief summary: This study allows to evaluate the strength and duration of immune responses between annual receipt of standard inactivated vaccine and alternative potent vaccines, including annual receipt of adjuvanted inactivated vaccine, annual receipt of high-dose inactivated vaccine, annual receipt of recombinant HA vaccine, and the alternate combinations of the former three vaccines over four years, for identifying improved vaccination strategies for influenza vaccination in older adults in a location experiencing a subtropical pattern in influenza activity.

Detailed description: Background: The typical vaccination strategy of annual administration with inactivated trivalent influenza vaccine (TIV) or quadrivalent influenza vaccine (QIV) may provide suboptimal protection to older adults in a location with prolonged periods of influenza activity because of the weaker immune response of older adults to vaccination and because of post-vaccination waning in protection over the course of a year. We hypothesize that in a subtropical or tropical location with prolonged circulation of influenza viruses, the higher antibody titers over years achieved after receipt of annual high-dose vaccine, MF59-adjuvanted vaccine or recombinant haemagglutinin (HA) vaccine, or different vaccination strategies of their combinations with or without the standard vaccine, might lead to greater protection than annual receipt of standard vaccines.

Aim: To test the immune profiles over time of older adults following different influenza vaccination strategies.

Design and subjects: Initially a 4-year immunogenicity study with a randomized controlled design among 2200 older adults aged 65-82 years. We will enroll participants who are willing to receive annual influenza vaccination from the general community including community centres and day-care centres. Eligible individuals will be randomly allocated to ten intervention groups (i.e. annual standard QIV, annual MF59-adjuvanted TIV, annual high-dose TIV, annual recombinant-HA QIV, and six combinations of their alternate annual use) consisting of four rounds of vaccination before each winter influenza season and followed up for 4 years. For each round of vaccination, blood samples for immunological tests will be collected before vaccination and 30 and 182 days after vaccination in all participants, and also at 7, 91 and 273 days after vaccination in a subset of 10% of the participants. Acute illnesses among participants will be monitored by active surveillance efforts during influenza seasons. The vaccine formulation in each round of vaccination will be updated for each season according to WHO recommendations.

Study extension: In years 5-8, all participants will receive the recombinant-HA QIV once per year before each winter influenza season, and their receipt of COVID-19 vaccines will also be recorded. Samples will be collected at the same timepoints to monitor immune responses to influenza vaccination and how responses are affected by prior vaccination history.

Main outcome measures: Antibody titers measured by haemagglutination-inhibition assays, which is an established correlate of protection, in addition to other measurements on humoral and cell-mediated immune responses in the ten intervention groups each year.

Eligibility criteria: Inclusion Criteria:

• Adult aged 65-82 years attending ECC and EDC who has not received 2017/18 seasonal influenza vaccine and is willing to receive annual influenza vaccination

Exclusion Criteria:

* Individuals who show signs of dementia (do not pass the Mini-cog test under Appendix 1a: Recruitment Screening Log) or significant cognitive impairment and are not competent to give their consent.
* Individuals who report medical conditions not suitable to receive inactivated influenza vaccines, such as:

  * Severe allergic reaction (e.g., anaphylaxis) after previous dose of any influenza vaccine; or to a vaccine component, including egg protein;
  * Moderate or severe acute illness with or without fever after any previous influenza vaccination; or
  * A history of Guillain-Barré syndrome (GBS) within 6 weeks of previous influenza vaccination.
* Individuals, who report medical conditions not suitable to receive intramuscular injection, such as:

  * bleeding disorders
  * habitually taking anticoagulants (with the exception of antiplatelets such as aspirin).
* Individuals who have any medical conditions not suitable to receive inactivated influenza vaccines as determined by a clinician.

Primary outcomes:
measure: Difference in antibody titres
timeFrame: 30 and 182 days after each vaccination
Secondary outcomes:
measure: Seroprotection
timeFrame: 30 days after each vaccination
measure: CMI responses
timeFrame: . 7 days after each vaccination
measure: Adverse events
timeFrame: 30 days after each vaccination
measure: PCR confirmed infection
timeFrame: 182 days after each vaccination
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: The University of Hong Kong
Study officials:
affiliation: The University of Hong Kong
name: Benjamin J COWLING, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cowling BJ, Thompson MG, Ng TWY, Fang VJ, Perera RAPM, Leung NHL, Chen Y, So HC, Ip DKM, Iuliano AD. Comparative Reactogenicity of Enhanced Influenza Vaccines in Older Adults. J Infect Dis. 2020 Sep 14;222(8):1383-1391. doi: 10.1093/infdis/jiaa255.
citation: Cowling BJ, Perera RAPM, Valkenburg SA, Leung NHL, Iuliano AD, Tam YH, Wong JHF, Fang VJ, Li APY, So HC, Ip DKM, Azziz-Baumgartner E, Fry AM, Levine MZ, Gangappa S, Sambhara S, Barr IG, Skowronski DM, Peiris JSM, Thompson MG. Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial. Clin Infect Dis. 2020 Oct 23;71(7):1704-1714. doi: 10.1093/cid/ciz1034.