FluPhase 4NCT03694808

FLUAD vs. FLUZONE HD Influenza Vaccine in Residents of Long Term Care

A Phase 4 study testing Fluad Vaccine and Fluzone HD Vaccine in people with Flu, run by David H. Canaday at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Adjuvanted flu vaccine, Fluad, is not immunologically inferior to HD influenza vaccine in older persons living in long-term care. Read more about this study

Who is it for?: Ages 65 years and older
Conditions the study is for: Flu
What is being tested?: Fluad Vaccine and Fluzone HD Vaccine
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 478 participants
Where: 2 sitesUnited States
Study dates: 23 Sep 2018to 31 Jan 2023
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 years and older
All sexes
No healthy volunteers
Older adult

Who may be able to join

> 65 years old
Able to obtain consent from subject or legally authorized representative (subject to provide assent if cognitively/physically able to do so)
Able to participate throughout the study period

Who cannot join

Recent illness (within 30 days) severe enough to require hospitalization or physician-directed outpatient pharmacotherapy
Administration of immunomodulatory agents (e.g. oral corticosteroids except prednisone < 10 mg daily, cyclosporine, and biologics (DMARDS) for Rheumatologic/Dermatologic conditions) in the last 3 months
Cancer requiring treatment in the past three years, except for non- melanoma skin cancers or cancers that have clearly been cured or carry an excellent prognosis including prostate cancer.
Myocardial infarction, major heart surgery (i.e. valve replacement or bypass surgery), stroke, deep vein thrombosis or pulmonary embolus in the past 4 months
Allergies or history of significant adverse reactions to any component of influenza vaccine including egg protein and latex or after a previous dose of any influenza vaccine.
History of Guillian-Barré Syndrome within 6 weeks of a prior influenza vaccine.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Louis Stokes Cleveland VA Medical Center
Cleveland, Ohio, 44106
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106

Other trials in United States

About this study

Official title: Non-inferiority Study of Adjuvanted vs. High Dose Flu Vaccine in Residents of Long Term Care

Adjuvanted flu vaccine, Fluad, is not immunologically inferior to HD influenza vaccine in older persons living in long-term care.

Read the detailed description

As the primary endpoint, this trial is be using pre- to post-vaccine changes in HAI titers to compare seroconversion rates and post-vaccination HAI titers to calculate the ratio of the geometric mean titers in the two treatment groups. HAI is an in vitro bioassay that determines a subject's serum levels of anti-influenza antibodies. The FDA uses this as a standard immunogenicity assay for licensure. The trial will follow guidelines set out in the FDA guidance document discussing non-inferiority immunogenicity studies. As additional methods to assess immunogenicity, an assessment of anti-NA by performing NA inhibition assays (NAI) and SVN assays will be added. A recent trial supported the use of NAI and SVN assays as a correlate for protection in a trial of geriatric subjects. A healthy human challenge model showed that NAI is more predictive of protection and reduced disease than HAI

In the large HD vaccine clinical efficacy trial (n=31,989) one third of subjects also had immunogenicity data that allowed looking for correlations of immune assays with protection. Their conclusions were that HAI and other immune assays are potential correlates of influenza vaccine protection in older adults, and that the protective thresholds for the HAI assay in the elderly appear consistent with those previously described for younger adults, provided the assay virus matches the circulating virus.

Significance Data compiled by CDC in 2011-2012 showed that there were 1,383,700 residents in NHs. Also about 4,742,500 patients received services from home health agencies, and 1,244,500 patients received services from hospices, collectively accounting for much of the frailest in the US. Overall, these provider sectors served over 8 million people annually (2013). This study will focus on residents in NHs but the findings of this study are highly relevant to persons frail enough to require such services in all of settings where the vast majority are at least 65 years old and thus appropriate for Fluad or HD, influenza vaccines licensed for this age group.

The SD influenza vaccine has diminished efficacy in the older population with the more debilitated LTC residents being among the worst responders yet with the highest mortality. Deaths due to pneumonia and influenza and chronic lung disease were 20 times higher among NH residents compared to community residents. The current availability of two vaccines specifically for the elderly that both appear to work better than SD vaccine begs the question: is the newer and less-costly Fluad vaccine non-inferior or even superior to HD vaccine? The proposed study aims to initially address non-inferiority using immunologic endpoints as this is feasible in the clinical trial R01 grant structure and a critical first step to obtain head-to-head data from the same trial, cohort and vaccine years. This proposed study itself may provide direct guidance on vaccine usage or inform a future trial assessing actual superiority should that be appropriate based on the results of this study.

HD vaccine is increasingly used by older Americans despite its greater cost over the SD vaccine and no preferential recommendation by the Advisory Committee on Immunization Practices (ACIP), the CDC committee responsible for making the vaccine recommendations for the U.S. A finding of non-inferiority in the primary endpoint would provide a strong rationale to consider using Fluad over HD that could result in some cost avoidance across large long-term care system in the U.S. The trial is not powered for a superiority analysis but in a non-inferiority trial if the findings are substantial enough they may show superiority.

In the normal seasonal setting, influenza strains drift antigenically and therefore vary from year to year. The CDC's prediction many months before the vaccination season sets the composition for the next season's vaccine, but does not always correctly anticipate the exact strain match that eventually actually circulates. There are Medicare claims data and modeling in the NH population that there is a significant increase in death and hospitalization in bad match over good match years particularly when A/H3N2 predominates. In those mismatched years in particular, heterologous immunity or immunity to other non-exact match strains becomes much more important if the vaccine is going to provide any benefit that season. Fluad is an adjuvanted vaccine that has been shown to have a more broad-based or heterologous immunity than SD vaccine that is not adjuvanted. HD is also not adjuvanted. Broad based immunity is especially desirable for A/H3N2 immunity as that has had 4 different circulating strains in the last 5 years while circulating A/H1N1 has been the same for 5 years; i.e., vaccine mismatch is more likely with the A/H3N2 circulating strain. A/H3N2 is associated with the majority of influenza hospitalizations and death among the elderly.

Conditions: Flu
Being tested: Fluad Vaccine, Fluzone HD Vaccine
Keywords: Flu, Vaccine
Medical subject headings: Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Fluad VaccineDrug
single adjuvanted dose (AD) intramuscular injection
Fluzone HD VaccineDrug
single high dose (HD) intramuscular injection

Study groups in NCT03694808
Study group	Role	What they receive
Fluad Vaccine	Active comparator	A single adjuvanted dose (AD) intramuscular injection Receives: Drug: Fluad Vaccine
Fluzone Vaccine	Active comparator	A single high dose (HD) intramuscular injection Receives: Drug: Fluzone HD Vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall Hemagglutinin Inhibition (HAI) H1N1 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
HAI is an in vitro bioassay testing subjects' sera for specific anti-influenza antibodies to each strain in the vaccine. Seroconversion is 4-fold rise in antibody titer. The FDA uses this as the standard immunogenicity assay for licensure. The investigators will follow the guidelines set out in the FDA guidance document on non-inferiority immunogenicity studies for the analysis plan.
Measured: 1 month post vaccine administration
Overall Hemagglutinin Inhibition (HAI) H3N2 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
HAI is an in vitro bioassay testing subjects' sera for specific anti-influenza antibodies to each strain in the vaccine. Seroconversion is 4-fold rise in antibody titer. The FDA uses this as the standard immunogenicity assay for licensure. The investigators will follow the guidelines set out in the FDA guidance document on non-inferiority immunogenicity studies for the analysis plan.
Measured: 1 month post vaccine administration
Overall Hemagglutinin Inhibition (HAI) B Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
HAI is an in vitro bioassay testing subjects' sera for specific anti-influenza antibodies to each strain in the vaccine. Seroconversion is 4-fold rise in antibody titer. The FDA uses this as the standard immunogenicity assay for licensure. The investigators will follow the guidelines set out in the FDA guidance document on non-inferiority immunogenicity studies for the analysis plan.
Measured: 1 month post vaccine administration
Overall HAI H1N1 Seroconversion Rate Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
HAI is an in vitro bioassay testing subjects' sera for specific anti-influenza antibodies to each strain in the vaccine. Seroconversion is 4-fold rise in antibody titer. The FDA uses this as the standard immunogenicity assay for licensure. The investigators will follow the guidelines set out in the FDA guidance document on non-inferiority immunogenicity studies for the analysis plan.
Measured: 1 month post vaccine administration
Overall HAI H3N2 Seroconversion Rate Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
HAI is an in vitro bioassay testing subjects' sera for specific anti-influenza antibodies to each strain in the vaccine. Seroconversion is 4-fold rise in antibody titer. The FDA uses this as the standard immunogenicity assay for licensure. The investigators will follow the guidelines set out in the FDA guidance document on non-inferiority immunogenicity studies for the analysis plan.
Measured: 1 month post vaccine administration
Overall HAI B Seroconversion Rate Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
HAI is an in vitro bioassay testing subjects' sera for specific anti-influenza antibodies to each strain in the vaccine. Seroconversion is 4-fold rise in antibody titer. The FDA uses this as the standard immunogenicity assay for licensure. The investigators will follow the guidelines set out in the FDA guidance document on non-inferiority immunogenicity studies for the analysis plan.
Measured: 1 month post vaccine administration

Secondary outcomes (9)

Overall Neuraminidase Inhibition (NAI) H1N1 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Neuraminidase inhibition (NAI) assays will be performed to measure anti-neuraminidase titers. Seroconversion is 4-fold rise in antibody titer.
Measured: 1 month post vaccine administration
Overall Neuraminidase Inhibition (NAI) H3N2 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Neuraminidase inhibition (NAI) assays will be performed to measure anti-neuraminidase titers. Seroconversion is 4-fold rise in antibody titer.
Measured: 1 month post vaccine administration
Overall H1N1 NAI Seroconversion Rate Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Neuraminidase inhibition (NAI) assays will be performed to measure anti-neuraminidase titers. Seroconversion is 4-fold rise in antibody titer.
Measured: 1 month post vaccine administration
Overall NAI H3N2 Seroconversion Rate Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Neuraminidase inhibition (NAI) assays will be performed to measure anti-neuraminidase titers. Seroconversion is 4-fold rise in antibody titer.
Measured: 1 month post vaccine administration
Overall Serum Virus Neutralization (SVN) H1N1 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Serum virus neutralization (SVN) assays will be performed to measure the ability of serum to inhibit influenza infection.
Measured: 1 month post vaccine administration
Heterologous Immunity at 1 Month Post-vaccination Will be Compared Between FLUAD and FLUZONE HD.
Hemagglutinin inhibition (HAI), neuraminidase inhibition (NAI) assays and serum virus neutralization (SVN) assays will be performed with heterologous A/H3N2 strains to determine if Fluad has an increased breadth of both B and T cell responses as would be predicted from an adjuvanted vaccine.
Measured: 1 month post vaccine administration
Overall Serum Virus Neutralization (SVN) H3N2 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Serum virus neutralization (SVN) assays will be performed to measure the ability of serum to inhibit influenza infection.
Measured: 1 month post vaccine administration
Overall Serum Virus Neutralization (SVN) H1N1 Seroconversion Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Serum virus neutralization (SVN) assays will be performed to measure the ability of serum to inhibit influenza infection.
Measured: 1 month post vaccine administration
Overall Serum Virus Neutralization (SVN) H3N2 Seroconversion Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Serum virus neutralization (SVN) assays will be performed to measure the ability of serum to inhibit influenza infection.
Measured: 1 month post vaccine administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Sep 201831 Jan 2023

First posted3 Oct 2018
Study start23 Sep 2018
Primary completion31 Jan 2023
Study completion31 Jan 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (19)Papers the sponsor has linked to this study.
Other trials for FluStudies of the same condition, open and under way.
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: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: A non-inferiority randomized clinical trial to enroll 500 long term care (LTC) dwellers from at least one of 40 nursing homes sites in northern Ohio. Age 65 and older to receive either Fluad or HD vaccine at 1:1 ratio. Blood will be sampled pre- and post-vaccine and post-influenza season and coded for blinded laboratory analysis. Randomization by from randomizer.org software./RedCAP
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 478 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03694808
Sponsor's protocol ID: 10-27-29
Other IDs: 1R01AI129709-01A1
Status last verified: Apr 2024
First submitted: 26 Sep 2018
Last updated: 30 Apr 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Ansaldi F, Bacilieri S, Durando P, Sticchi L, Valle L, Montomoli E, Icardi G, Gasparini R, Crovari P. Cross-protection by MF59-adjuvanted influenza vaccine: neutralizing and haemagglutination-inhibiting antibody activity against A(H3N2) drifted influenza viruses. Vaccine. 2008 Mar 17;26(12):1525-9. doi: 10.1016/j.vaccine.2008.01.019. Epub 2008 Feb 1.
PubMed 18294741
Centers for Disease Control and Prevention (CDC). Estimates of deaths associated with seasonal influenza --- United States, 1976-2007. MMWR Morb Mortal Wkly Rep. 2010 Aug 27;59(33):1057-62.
PubMed 20798667
DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, Pollak R, Christoff J, Earl J, Landolfi V, Martin E, Gurunathan S, Nathan R, Greenberg DP, Tornieporth NG, Decker MD, Talbot HK. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014 Aug 14;371(7):635-45. doi: 10.1056/NEJMoa1315727.
PubMed 25119609
Dunning AJ, DiazGranados CA, Voloshen T, Hu B, Landolfi VA, Talbot HK. Correlates of Protection against Influenza in the Elderly: Results from an Influenza Vaccine Efficacy Trial. Clin Vaccine Immunol. 2016 Jan 13;23(3):228-35. doi: 10.1128/CVI.00604-15.
PubMed 26762363
Falsey AR, Treanor JJ, Tornieporth N, Capellan J, Gorse GJ. Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older. J Infect Dis. 2009 Jul 15;200(2):172-80. doi: 10.1086/599790.
PubMed 19508159
Frey SE, Reyes MR, Reynales H, Bermal NN, Nicolay U, Narasimhan V, Forleo-Neto E, Arora AK. Comparison of the safety and immunogenicity of an MF59(R)-adjuvanted with a non-adjuvanted seasonal influenza vaccine in elderly subjects. Vaccine. 2014 Sep 3;32(39):5027-34. doi: 10.1016/j.vaccine.2014.07.013. Epub 2014 Jul 18.
PubMed 25045825
Hancock K, Veguilla V, Lu X, Zhong W, Butler EN, Sun H, Liu F, Dong L, DeVos JR, Gargiullo PM, Brammer TL, Cox NJ, Tumpey TM, Katz JM. Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med. 2009 Nov 12;361(20):1945-52. doi: 10.1056/NEJMoa0906453. Epub 2009 Sep 10.
PubMed 19745214
Iob A, Brianti G, Zamparo E, Gallo T. Evidence of increased clinical protection of an MF59-adjuvant influenza vaccine compared to a non-adjuvant vaccine among elderly residents of long-term care facilities in Italy. Epidemiol Infect. 2005 Aug;133(4):687-93. doi: 10.1017/s0950268805003936.
PubMed 16050515
Izurieta HS, Thadani N, Shay DK, Lu Y, Maurer A, Foppa IM, Franks R, Pratt D, Forshee RA, MaCurdy T, Worrall C, Howery AE, Kelman J. Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis. Lancet Infect Dis. 2015 Mar;15(3):293-300. doi: 10.1016/S1473-3099(14)71087-4. Epub 2015 Feb 9.
PubMed 25672568
Izurieta HS, Thadani N, Shay DK. Corrections. Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis. Lancet Infect Dis. 2015 Mar;15(3):263. doi: 10.1016/S1473-3099(15)70070-8. No abstract available.
PubMed 25749223
Mannino S, Villa M, Apolone G, Weiss NS, Groth N, Aquino I, Boldori L, Caramaschi F, Gattinoni A, Malchiodi G, Rothman KJ. Effectiveness of adjuvanted influenza vaccination in elderly subjects in northern Italy. Am J Epidemiol. 2012 Sep 15;176(6):527-33. doi: 10.1093/aje/kws313. Epub 2012 Aug 31.
PubMed 22940713
Memoli MJ, Shaw PA, Han A, Czajkowski L, Reed S, Athota R, Bristol T, Fargis S, Risos K, Powers JH, Davey RT Jr, Taubenberger JK. Evaluation of Antihemagglutinin and Antineuraminidase Antibodies as Correlates of Protection in an Influenza A/H1N1 Virus Healthy Human Challenge Model. mBio. 2016 Apr 19;7(2):e00417-16. doi: 10.1128/mBio.00417-16.
PubMed 27094330
Menec VH, MacWilliam L, Aoki FY. Hospitalizations and deaths due to respiratory illnesses during influenza seasons: a comparison of community residents, senior housing residents, and nursing home residents. J Gerontol A Biol Sci Med Sci. 2002 Oct;57(10):M629-35. doi: 10.1093/gerona/57.10.m629.
PubMed 12242314
Pop-Vicas A, Rahman M, Gozalo PL, Gravenstein S, Mor V. Estimating the Effect of Influenza Vaccination on Nursing Home Residents' Morbidity and Mortality. J Am Geriatr Soc. 2015 Sep;63(9):1798-804. doi: 10.1111/jgs.13617. Epub 2015 Aug 17.
PubMed 26280675
Richardson DM, Medvedeva EL, Roberts CB, Linkin DR; Centers for Disease Control and Prevention Epicenter Program. Comparative effectiveness of high-dose versus standard-dose influenza vaccination in community-dwelling veterans. Clin Infect Dis. 2015 Jul 15;61(2):171-6. doi: 10.1093/cid/civ261. Epub 2015 Mar 31.
PubMed 25829001

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 30 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Non-inferiority Study of Adjuvanted vs. High Dose Flu Vaccine in Residents of Long Term Care
ClinicalTrials.gov ID: NCT03694808
Acronym / sponsor ID: 10-27-29
Conditions: Flu
Keywords: Flu, Vaccine
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 478 participants (actual)
Lead sponsor: David H. CanadayUniversity, hospital or other
Collaborators: Case Western Reserve University, US Department of Veterans Affairs, Brown University, National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID)
Study start: 23 Sep 2018 (actual)
Primary completion: 31 Jan 2023 (actual)
Study completion: 31 Jan 2023 (actual)
First posted: 3 Oct 2018 (actual)
Results: Posted 30 Apr 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Adjuvanted flu vaccine, Fluad, is not immunologically inferior to HD influenza vaccine in older persons living in long-term care.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2
Model description: A non-inferiority randomized clinical trial to enroll 500 long term care (LTC) dwellers from at least one of 40 nursing homes sites in northern Ohio. Age 65 and older to receive either Fluad or HD vaccine at 1:1 ratio. Blood will be sampled pre- and post-vaccine and post-influenza season and coded for blinded laboratory analysis. Randomization by from randomizer.org software./RedCAP

Arm	Type	Receives
Fluad Vaccine	Active comparator	Drug: Fluad VaccineA single adjuvanted dose (AD) intramuscular injection
Fluzone Vaccine	Active comparator	Drug: Fluzone HD VaccineA single high dose (HD) intramuscular injection

Who may qualify

Ages: 65 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Older adult

Key inclusion criteria (3 listed)

> 65 years old
Able to obtain consent from subject or legally authorized representative (subject to provide assent if cognitively/physically able to do so)
Able to participate throughout the study period

Key exclusion criteria (6 listed)

Recent illness (within 30 days) severe enough to require hospitalization or physician-directed outpatient pharmacotherapy
Administration of immunomodulatory agents (e.g. oral corticosteroids except prednisone < 10 mg daily, cyclosporine, and biologics (DMARDS) for Rheumatologic/Dermatologic conditions) in the last 3 months
Cancer requiring treatment in the past three years, except for non- melanoma skin cancers or cancers that have clearly been cured or carry an excellent prognosis including prostate cancer.
Myocardial infarction, major heart surgery (i.e. valve replacement or bypass surgery), stroke, deep vein thrombosis or pulmonary embolus in the past 4 months
Allergies or history of significant adverse reactions to any component of influenza vaccine including egg protein and latex or after a previous dose of any influenza vaccine.

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
Fluad Vaccinesingle adjuvanted dose (AD) intramuscular injection	Drug	Fluad Vaccine
Fluzone HD Vaccinesingle high dose (HD) intramuscular injection	Drug	Fluzone Vaccine

Primary outcome

Overall Hemagglutinin Inhibition (HAI) H1N1 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Time frame: 1 month post vaccine administration
HAI is an in vitro bioassay testing subjects' sera for specific anti-influenza antibodies to each strain in the vaccine. Seroconversion is 4-fold rise in antibody titer. The FDA uses this as the standard immunogenicity assay for licensure. The investigators will follow the guidelines set out in the FDA guidance document on non-inferiority immunogenicity studies for the analysis plan.
Overall Hemagglutinin Inhibition (HAI) H3N2 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Time frame: 1 month post vaccine administration
HAI is an in vitro bioassay testing subjects' sera for specific anti-influenza antibodies to each strain in the vaccine. Seroconversion is 4-fold rise in antibody titer. The FDA uses this as the standard immunogenicity assay for licensure. The investigators will follow the guidelines set out in the FDA guidance document on non-inferiority immunogenicity studies for the analysis plan.
Overall Hemagglutinin Inhibition (HAI) B Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Time frame: 1 month post vaccine administration
HAI is an in vitro bioassay testing subjects' sera for specific anti-influenza antibodies to each strain in the vaccine. Seroconversion is 4-fold rise in antibody titer. The FDA uses this as the standard immunogenicity assay for licensure. The investigators will follow the guidelines set out in the FDA guidance document on non-inferiority immunogenicity studies for the analysis plan.
Overall HAI H1N1 Seroconversion Rate Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Time frame: 1 month post vaccine administration
HAI is an in vitro bioassay testing subjects' sera for specific anti-influenza antibodies to each strain in the vaccine. Seroconversion is 4-fold rise in antibody titer. The FDA uses this as the standard immunogenicity assay for licensure. The investigators will follow the guidelines set out in the FDA guidance document on non-inferiority immunogenicity studies for the analysis plan.
Overall HAI H3N2 Seroconversion Rate Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Time frame: 1 month post vaccine administration
HAI is an in vitro bioassay testing subjects' sera for specific anti-influenza antibodies to each strain in the vaccine. Seroconversion is 4-fold rise in antibody titer. The FDA uses this as the standard immunogenicity assay for licensure. The investigators will follow the guidelines set out in the FDA guidance document on non-inferiority immunogenicity studies for the analysis plan.
Overall HAI B Seroconversion Rate Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Time frame: 1 month post vaccine administration
HAI is an in vitro bioassay testing subjects' sera for specific anti-influenza antibodies to each strain in the vaccine. Seroconversion is 4-fold rise in antibody titer. The FDA uses this as the standard immunogenicity assay for licensure. The investigators will follow the guidelines set out in the FDA guidance document on non-inferiority immunogenicity studies for the analysis plan.

9 secondary outcomes

Overall Neuraminidase Inhibition (NAI) H1N1 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Time frame: 1 month post vaccine administration
Overall Neuraminidase Inhibition (NAI) H3N2 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Time frame: 1 month post vaccine administration
Overall H1N1 NAI Seroconversion Rate Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Time frame: 1 month post vaccine administration
Overall NAI H3N2 Seroconversion Rate Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Time frame: 1 month post vaccine administration
Overall Serum Virus Neutralization (SVN) H1N1 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Time frame: 1 month post vaccine administration
Heterologous Immunity at 1 Month Post-vaccination Will be Compared Between FLUAD and FLUZONE HD.
Time frame: 1 month post vaccine administration
Overall Serum Virus Neutralization (SVN) H3N2 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Time frame: 1 month post vaccine administration
Overall Serum Virus Neutralization (SVN) H1N1 Seroconversion Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Time frame: 1 month post vaccine administration
Overall Serum Virus Neutralization (SVN) H3N2 Seroconversion Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.
Time frame: 1 month post vaccine administration

Results and safety

Results posted to the registry on 30 Apr 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Fluad Vaccine	240	194
Fluzone Vaccine	219	193

Primary outcome: Overall Hemagglutinin Inhibition (HAI) H1N1 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.

Time frame: 1 month post vaccine administration. Geometric mean (95% Confidence Interval). Unit: Titer

Measure	Fluad Vaccine n = 192	Fluzone Vaccine n = 190
Year 1 (2018-2019)	213.4 (156.9 to 290.4)	261.9 (192.3 to 356.6)
Year 2 (2019-2020)	70.5 (53.5 to 92.9)	67.2 (52.3 to 86.3)

Fluad Vaccine vs Fluzone Vaccine: ratio of GMT (Fluzone/Fluad): 1.23 (95% CI 0.8 to 1.89), t-test, 2 sided
Fluad Vaccine vs Fluzone Vaccine: Ratio of GMT (Fluzone/Fluad): 0.95 (95% CI 0.66 to 1.38), t-test, 2 sided

Population analysed: The total number analyzed represents the overall number of participants per group analyzed for both years combined. The total number analyzed per year is represented in the row value.

Primary outcome: Overall Hemagglutinin Inhibition (HAI) H3N2 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.

Time frame: 1 month post vaccine administration. Geometric mean (95% Confidence Interval). Unit: Titer

Measure	Fluad Vaccine n = 194	Fluzone Vaccine n = 193
Year 1 (2018-2019)	375.5 (271.3 to 519.7)	517.3 (380.8 to 702.6)
Year 2 (2019-2020)	140.2 (96.9 to 202.7)	120.4 (87.2 to 166.2)

Fluad Vaccine vs Fluzone Vaccine: Ratio of GMT (Fluzone/Fluad): 1.38 (95% CI 0.88 to 2.15), t-test, 2 sided
Fluad Vaccine vs Fluzone Vaccine: Ratio of GMT (Fluzone/Fluad): 0.86 (95% CI 0.53 to 1.4), t-test, 2 sided

Primary outcome: Overall Hemagglutinin Inhibition (HAI) B Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.

Time frame: 1 month post vaccine administration. Geometric mean (95% Confidence Interval). Unit: Titer

Measure	Fluad Vaccine n = 194	Fluzone Vaccine n = 193
Year 1 (2018-2019)	113.6 (87.6 to 146.8)	210.4 (152.5 to 290.3)
Year 2 (2019-2020)	75.5 (58.1 to 98.1)	66.1 (51.1 to 85.5)

Fluad Vaccine vs Fluzone Vaccine: Ratio of GMT (Fluzone/Fluad): 1.85 (95% CI 1.23 to 2.79), t-test, 2 sided
Fluad Vaccine vs Fluzone Vaccine: Ratio of GMT (Fluzone/Fluad): 0.88 (95% CI 0.61 to 1.26), t-test, 2 sided

Primary outcome: Overall HAI H1N1 Seroconversion Rate Between FLUAD and FLUZONE HD at 1 Month Post-vaccination.

Time frame: 1 month post vaccine administration. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Fluad Vaccine n = 192	Fluzone Vaccine n = 190
Year 1 (2018-2019)	29.2 (20.3 to 40)	44.6 (33.8 to 55.9)
Year 2 (2019-2020)	48.5 (38.7 to 58.5)	43 (33.6 to 52.9)

Fluad Vaccine vs Fluzone Vaccine: Difference in proportions: 0.154 (95% CI -0.001 to 0.308), Test of proportions
Fluad Vaccine vs Fluzone Vaccine: Difference in proportions: -0.056 (95% CI -0.2 to 0.089), Test of proportions

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-Cause Mortality was only monitored/assessed two weeks following the final blood draw (up to 8 months post vaccine administration). Serious and Other (Not Including Serious) Adverse Events were not monitored/assessed.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Fluad Vaccine	0 of 0	0 of 0	1 of 194
Fluzone Vaccine	0 of 0	0 of 0	1 of 193

Limitations and caveats (from the sponsor): 1. For all SVN related outcomes (11, 13, 14, 15) data was only collected for the 2018-2019 season 2. \>38% of values are at upper limit of detection (25% of Day 0 and \>50% of Day 28 values) Thus, the assay fails to capture any variability in values \> 1000. Given how many subjects have values in this range, we are unable to accurately summarize group differences; and a seroconversion endpoint that requires measuring change from d0 to d28 cannot be validly measured given this limitation.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 18294741Ansaldi F, Bacilieri S, Durando P, Sticchi L, Valle L, Montomoli E, Icardi G, Gasparini R, Crovari P. Cross-protection by MF59-adjuvanted influenza vaccine: neutralizing and haemagglutination-inhibiting antibody activity against A(H3N2) drifted influenza viruses. Vaccine. 2008 Mar 17;26(12):1525-9. doi: 10.1016/j.vaccine.2008.01.019. Epub 2008 Feb 1.
Background: PubMed 20798667Centers for Disease Control and Prevention (CDC). Estimates of deaths associated with seasonal influenza --- United States, 1976-2007. MMWR Morb Mortal Wkly Rep. 2010 Aug 27;59(33):1057-62.
Background: PubMed 25119609DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, Pollak R, Christoff J, Earl J, Landolfi V, Martin E, Gurunathan S, Nathan R, Greenberg DP, Tornieporth NG, Decker MD, Talbot HK. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014 Aug 14;371(7):635-45. doi: 10.1056/NEJMoa1315727.
Background: PubMed 26762363Dunning AJ, DiazGranados CA, Voloshen T, Hu B, Landolfi VA, Talbot HK. Correlates of Protection against Influenza in the Elderly: Results from an Influenza Vaccine Efficacy Trial. Clin Vaccine Immunol. 2016 Jan 13;23(3):228-35. doi: 10.1128/CVI.00604-15.
Background: PubMed 19508159Falsey AR, Treanor JJ, Tornieporth N, Capellan J, Gorse GJ. Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older. J Infect Dis. 2009 Jul 15;200(2):172-80. doi: 10.1086/599790.
Background: PubMed 25045825Frey SE, Reyes MR, Reynales H, Bermal NN, Nicolay U, Narasimhan V, Forleo-Neto E, Arora AK. Comparison of the safety and immunogenicity of an MF59(R)-adjuvanted with a non-adjuvanted seasonal influenza vaccine in elderly subjects. Vaccine. 2014 Sep 3;32(39):5027-34. doi: 10.1016/j.vaccine.2014.07.013. Epub 2014 Jul 18.
Background: PubMed 19745214Hancock K, Veguilla V, Lu X, Zhong W, Butler EN, Sun H, Liu F, Dong L, DeVos JR, Gargiullo PM, Brammer TL, Cox NJ, Tumpey TM, Katz JM. Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med. 2009 Nov 12;361(20):1945-52. doi: 10.1056/NEJMoa0906453. Epub 2009 Sep 10.
Background: PubMed 16050515Iob A, Brianti G, Zamparo E, Gallo T. Evidence of increased clinical protection of an MF59-adjuvant influenza vaccine compared to a non-adjuvant vaccine among elderly residents of long-term care facilities in Italy. Epidemiol Infect. 2005 Aug;133(4):687-93. doi: 10.1017/s0950268805003936.
Background: PubMed 25672568Izurieta HS, Thadani N, Shay DK, Lu Y, Maurer A, Foppa IM, Franks R, Pratt D, Forshee RA, MaCurdy T, Worrall C, Howery AE, Kelman J. Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis. Lancet Infect Dis. 2015 Mar;15(3):293-300. doi: 10.1016/S1473-3099(14)71087-4. Epub 2015 Feb 9.
Background: PubMed 25749223Izurieta HS, Thadani N, Shay DK. Corrections. Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis. Lancet Infect Dis. 2015 Mar;15(3):263. doi: 10.1016/S1473-3099(15)70070-8. No abstract available.
Background: PubMed 22940713Mannino S, Villa M, Apolone G, Weiss NS, Groth N, Aquino I, Boldori L, Caramaschi F, Gattinoni A, Malchiodi G, Rothman KJ. Effectiveness of adjuvanted influenza vaccination in elderly subjects in northern Italy. Am J Epidemiol. 2012 Sep 15;176(6):527-33. doi: 10.1093/aje/kws313. Epub 2012 Aug 31.
Background: PubMed 27094330Memoli MJ, Shaw PA, Han A, Czajkowski L, Reed S, Athota R, Bristol T, Fargis S, Risos K, Powers JH, Davey RT Jr, Taubenberger JK. Evaluation of Antihemagglutinin and Antineuraminidase Antibodies as Correlates of Protection in an Influenza A/H1N1 Virus Healthy Human Challenge Model. mBio. 2016 Apr 19;7(2):e00417-16. doi: 10.1128/mBio.00417-16.
Individual participant dataSharing planned: No

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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.

David Canaday, MD principal investigator

University Hospitals Cleveland Medical Center/Case Western Reserve University/Louis Stokes Cleveland VA Medical Center

Steven Gravenstein, MD, MPH principal investigator

Brown University and Providence VA Medical Center

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Fluad Vaccine and Fluzone HD Vaccine in people with Flu, run by David H. Canaday at 2 sites in United States.

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 3 inclusion and 6 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 30 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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?

Yes. Results are posted in the registry (first posted 30 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Overall Hemagglutinin Inhibition (HAI) H1N1 Titer Between FLUAD and FLUZONE HD at 1 Month Post-vaccination. (time frame: 1 month post vaccine administration). The study lists 6 primary outcomes in all. 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 NCT03694808, which also lists 19 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 30 Apr 2024.