Influenza, HumanPhase 4PIVOTNCT03330132
Immunogenicity of Alternative Annual Influenza Vaccination Strategies in Older Adults in Hong Kong
A Phase 4 study testing Standard inactivated influenza vaccine (NH formulation), MF 59 adjuvanted inactivated influenza vaccine (NH formulation) and High-dose inactivated influenza vaccine (NH formulation) in people with Influenza, Human, run by The University of Hong Kong at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 65 to 82 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza, Human
- What is being tested?
- Standard inactivated influenza vaccine (NH formulation), MF 59 adjuvanted inactivated influenza vaccine (NH formulation) and High-dose inactivated influenza vaccine (NH formulation)
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,861 participants
- Where
- 1 siteChina
- Study dates
- 7 Oct 2017to 31 Dec 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 82 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- 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
Who cannot join
- 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:
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Immunogenicity of Alternative Annual Influenza Vaccination Strategies in Older Adults in Hong Kong - a Randomized Controlled Trial
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.
Read the 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.
- Conditions
- Influenza, Human
- Being tested
- Standard inactivated influenza vaccine (NH formulation), MF 59 adjuvanted inactivated influenza vaccine (NH formulation), High-dose inactivated influenza vaccine (NH formulation), Recombinant hemagglutinin inactivated influenza vaccine (NH formulation)
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard inactivated influenza vaccine (NH formulation)Biological
0.5mL FluQuadri®, Sanofi Pasteur, containing 60μg antigen - 15μg for each influenza strain included - with strains recommended by the WHO for the northern hemisphere formulation.
MF 59 adjuvanted inactivated influenza vaccine (NH formulation)Biological
0.5mL FLUAD(TM), Seqirus containing 45μg antigen; 15μg for each influenza strain included and MF59C.1 adjuvant (MF59®) with strains recommended by the WHO for the northern hemisphere formulation.
High-dose inactivated influenza vaccine (NH formulation)Biological
0.5mL Fluzone® High-Dose, Sanofi Pasteur containing 180μg antigen; 60μg for each influenza strain included with strains recommended by the WHO for the northern hemisphere formulation.
Recombinant hemagglutinin inactivated influenza vaccine (NH formulation)Biological
0.5mL Flublok®, Protein Sciences Corporation containing 180μg antigen, 45μg for each influenza strain included with strains recommended by the WHO for the northern hemisphere formulation.
| Study group | Role | What they receive |
|---|---|---|
| Standard vaccine | Active comparator | Once-annual administration of standard vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. Receives: Biological: Standard inactivated influenza vaccine (NH formulation) |
| Alternating standard vaccine & adjuvanted vaccine | Experimental | Alternating once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. Receives: Biological: Standard inactivated influenza vaccine (NH formulation); Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation) |
| Alternating adjuvanted vaccine & standard vaccine | Experimental | Alternating once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. Receives: Biological: Standard inactivated influenza vaccine (NH formulation); Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation) |
| Alternating standard vaccine and high-dose vaccine | Experimental | Alternating once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. Receives: Biological: Standard inactivated influenza vaccine (NH formulation); Biological: High-dose inactivated influenza vaccine (NH formulation) |
| Alternating high-dose vaccine and standard vaccine | Experimental | Alternating once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. Receives: Biological: Standard inactivated influenza vaccine (NH formulation); Biological: High-dose inactivated influenza vaccine (NH formulation) |
| Alternating adjuvanted vaccine and high-dose vaccine | Experimental | Alternating once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. Receives: Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation); Biological: High-dose inactivated influenza vaccine (NH formulation) |
| Alternating high-dose vaccine and adjuvanted vaccine | Experimental | Alternating once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. Receives: Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation); Biological: High-dose inactivated influenza vaccine (NH formulation) |
| High-dose vaccine | Experimental | Once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. Receives: Biological: High-dose inactivated influenza vaccine (NH formulation) |
| Adjuvanted vaccine | Experimental | Once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. Receives: Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation) |
| Recombinant vaccine | Experimental | Once-annual administration of recombinant hemagglutinin inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. Receives: Biological: Recombinant hemagglutinin inactivated influenza vaccine (NH formulation) |
| Alternating recombinant vaccine and adjuvanted vaccine | Experimental | Alternating once-annual administration of recombinant hemagglutinin inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. Receives: Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation); Biological: Recombinant hemagglutinin inactivated influenza vaccine (NH formulation) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in antibody titres
The difference in antibody titres of participants measured by haemagglutination-inhibition (HAI) assay, evaluated by (1) the proportion of participants who achieve a target rise in antibody titre against each of the vaccine strains at 30 days, and (2) the geometric mean titre (GMT) ratios between the two groups against each of the vaccine strains at 30 days and 182 days. (The targeted rise in antibody titre is defined as the percentage of subjects with either a pre-vaccination HAI titre <10 and a post-vaccination HAI titre ≥40, or a pre-vaccination HAI titre ≥10 and a minimum four-fold rise in post-vaccination HAI antibody titre.)
Measured: 30 and 182 days after each vaccination
Secondary outcomes (4)
Seroprotection
The proportion of participants who achieve seroprotection defined as an HAI titre ≥40 after each vaccination before the winter seasons.
Measured: 30 days after each vaccination
CMI responses
The vaccine-induced influenza-specific CD4+ and CD8+ T cell responses 7 days post- vaccination, proxy by anti-viral IFNγ production evaluated by Intracellular Cytokine Staining (ICS) assay. Responses for these and other relevant biomarkers are compared to baseline at the time of vaccination.
Measured: . 7 days after each vaccination
Adverse events
The rate of adverse events within 30 days after vaccination for each round of vaccination.
Measured: 30 days after each vaccination
PCR confirmed infection
The rate of PCR-confirmed influenza infection in each round of the study.
Measured: 182 days after each vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start7 Oct 2017
- Primary completion31 Dec 2025
- Study completion31 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Influenza, HumanStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1,861 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Responsible party
- Sponsor
- Investigators
- Benjamin J COWLING, PhD, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03330132
- Sponsor's protocol ID
- YHT005.1
- Acronym
- PIVOT
- Status last verified
- Apr 2026
- First submitted
- 10 Oct 2017
- Last updated
- 15 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Daulagala P, Leung YWY, Luk LLH, Ho F, Chu SHN, Lin J, Cheng SMS, Leung NHL, Eichelberger MC, Peiris M, Iuliano AD, Thompson MG, Cowling BJ, Yen HL. Antineuraminidase Antibody Responses in Older Adults After Consecutive Vaccinations With Enhanced Influenza Vaccines: A Randomized Controlled Trial. J Infect Dis. 2026 Apr 29;233(4):e1022-e1030. doi: 10.1093/infdis/jiaf616.
PubMed 41359521Fox A, Sanchez-Ovando S, Carolan L, Hadiprodjo AJ, Chen Y, Ho F, Cheng SMS, Thompson MG, Iuliano AD, Levine MZ, Valkenburg SA, Ip DKM, Peiris JSM, Sullivan SG, Cowling BJ, Leung NHL. Enhanced Influenza Vaccines Extend A(H3N2) Antibody Reactivity in Older Adults but Prior Vaccination Effects Persist. Clin Infect Dis. 2025 Nov 6;81(4):e192-e201. doi: 10.1093/cid/ciaf060.
PubMed 40178253Cowling 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.
PubMed 32407535Cowling 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.
PubMed 31828291
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunogenicity of Alternative Annual Influenza Vaccination Strategies in Older Adults in Hong Kong - a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03330132
- Acronym / sponsor ID
- PIVOT / YHT005.1
- Conditions
- Influenza, Human
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,861 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Study start
- 7 Oct 2017 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 6 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 11
- 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
| Arm | Type | Receives |
|---|---|---|
| Standard vaccine | Active comparator | Biological: Standard inactivated influenza vaccine (NH formulation)Once-annual administration of standard vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. |
| Alternating standard vaccine & adjuvanted vaccine | Experimental | Biological: Standard inactivated influenza vaccine (NH formulation), Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation)Alternating once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. |
| Alternating adjuvanted vaccine & standard vaccine | Experimental | Biological: Standard inactivated influenza vaccine (NH formulation), Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation)Alternating once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. |
| Alternating standard vaccine and high-dose vaccine | Experimental | Biological: Standard inactivated influenza vaccine (NH formulation), Biological: High-dose inactivated influenza vaccine (NH formulation)Alternating once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. |
| Alternating high-dose vaccine and standard vaccine | Experimental | Biological: Standard inactivated influenza vaccine (NH formulation), Biological: High-dose inactivated influenza vaccine (NH formulation)Alternating once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. |
| Alternating adjuvanted vaccine and high-dose vaccine | Experimental | Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation), Biological: High-dose inactivated influenza vaccine (NH formulation)Alternating once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. |
| Alternating high-dose vaccine and adjuvanted vaccine | Experimental | Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation), Biological: High-dose inactivated influenza vaccine (NH formulation)Alternating once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. |
| High-dose vaccine | Experimental | Biological: High-dose inactivated influenza vaccine (NH formulation)Once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. |
| Adjuvanted vaccine | Experimental | Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation)Once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. |
| Recombinant vaccine | Experimental | Biological: Recombinant hemagglutinin inactivated influenza vaccine (NH formulation)Once-annual administration of recombinant hemagglutinin inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. |
| Alternating recombinant vaccine and adjuvanted vaccine | Experimental | Biological: MF 59 adjuvanted inactivated influenza vaccine (NH formulation), Biological: Recombinant hemagglutinin inactivated influenza vaccine (NH formulation)Alternating once-annual administration of recombinant hemagglutinin inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period. |
Who may qualify
- Ages
- 65 to 82 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (9 listed)
- 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:
- Individuals, who report medical conditions not suitable to receive intramuscular injection, such as:
- Individuals who have any medical conditions not suitable to receive inactivated influenza vaccines as determined by a clinician.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard inactivated influenza vaccine (NH formulation)0.5mL FluQuadri®, Sanofi Pasteur, containing 60μg antigen - 15μg for each influenza strain included - with strains recommended by the WHO for the northern hemisphere formulation. | Biological | Alternating adjuvanted vaccine & standard vaccine, Alternating high-dose vaccine and standard vaccine, Alternating standard vaccine & adjuvanted vaccine, Alternating standard vaccine and high-dose vaccine, Standard vaccine |
| MF 59 adjuvanted inactivated influenza vaccine (NH formulation)0.5mL FLUAD(TM), Seqirus containing 45μg antigen; 15μg for each influenza strain included and MF59C.1 adjuvant (MF59®) with strains recommended by the WHO for the northern hemisphere formulation. | Biological | Adjuvanted vaccine, Alternating adjuvanted vaccine & standard vaccine, Alternating adjuvanted vaccine and high-dose vaccine, Alternating high-dose vaccine and adjuvanted vaccine, Alternating recombinant vaccine and adjuvanted vaccine, Alternating standard vaccine & adjuvanted vaccine |
| High-dose inactivated influenza vaccine (NH formulation)0.5mL Fluzone® High-Dose, Sanofi Pasteur containing 180μg antigen; 60μg for each influenza strain included with strains recommended by the WHO for the northern hemisphere formulation. | Biological | Alternating adjuvanted vaccine and high-dose vaccine, Alternating high-dose vaccine and adjuvanted vaccine, Alternating high-dose vaccine and standard vaccine, Alternating standard vaccine and high-dose vaccine, High-dose vaccine |
| Recombinant hemagglutinin inactivated influenza vaccine (NH formulation)0.5mL Flublok®, Protein Sciences Corporation containing 180μg antigen, 45μg for each influenza strain included with strains recommended by the WHO for the northern hemisphere formulation. | Biological | Alternating recombinant vaccine and adjuvanted vaccine, Recombinant vaccine |
Primary outcome
Difference in antibody titres
Time frame: 30 and 182 days after each vaccination
The difference in antibody titres of participants measured by haemagglutination-inhibition (HAI) assay, evaluated by (1) the proportion of participants who achieve a target rise in antibody titre against each of the vaccine strains at 30 days, and (2) the geometric mean titre (GMT) ratios between the two groups against each of the vaccine strains at 30 days and 182 days. (The targeted rise in antibody titre is defined as the percentage of subjects with either a pre-vaccination HAI titre <10 and a post-vaccination HAI titre ≥40, or a pre-vaccination HAI titre ≥10 and a minimum four-fold rise in post-vaccination HAI antibody titre.)
4 secondary outcomes
Seroprotection
Time frame: 30 days after each vaccination
CMI responses
Time frame: . 7 days after each vaccination
Adverse events
Time frame: 30 days after each vaccination
PCR confirmed infection
Time frame: 182 days after each vaccination
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2026.
- Derived from this study: PubMed 41359521Daulagala P, Leung YWY, Luk LLH, Ho F, Chu SHN, Lin J, Cheng SMS, Leung NHL, Eichelberger MC, Peiris M, Iuliano AD, Thompson MG, Cowling BJ, Yen HL. Antineuraminidase Antibody Responses in Older Adults After Consecutive Vaccinations With Enhanced Influenza Vaccines: A Randomized Controlled Trial. J Infect Dis. 2026 Apr 29;233(4):e1022-e1030. doi: 10.1093/infdis/jiaf616.
- Derived from this study: PubMed 40178253Fox A, Sanchez-Ovando S, Carolan L, Hadiprodjo AJ, Chen Y, Ho F, Cheng SMS, Thompson MG, Iuliano AD, Levine MZ, Valkenburg SA, Ip DKM, Peiris JSM, Sullivan SG, Cowling BJ, Leung NHL. Enhanced Influenza Vaccines Extend A(H3N2) Antibody Reactivity in Older Adults but Prior Vaccination Effects Persist. Clin Infect Dis. 2025 Nov 6;81(4):e192-e201. doi: 10.1093/cid/ciaf060.
- Derived from this study: PubMed 32407535Cowling 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.
- Derived from this study: PubMed 31828291Cowling 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin J COWLING, PhD principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Standard inactivated influenza vaccine (NH formulation), MF 59 adjuvanted inactivated influenza vaccine (NH formulation) and High-dose inactivated influenza vaccine (NH formulation) in people with Influenza, Human, run by The University of Hong Kong at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in antibody titres (time frame: 30 and 182 days after each vaccination). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03330132, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2026; AzTrials last refreshed its copy on 8 Nov 2026.