Influenza Vaccine for Flu

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: British Columbia Centre for Disease Control

Must not be taking: Immune suppressants, Steroids

Disqualifiers: Immunodeficiency, Anaphylactic reaction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 1 day

55 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if your child is taking injected or oral steroids, they must not have taken them within the prior six weeks, except for nasal, topical, or inhaled steroids, which are allowed.

What data supports the effectiveness of the 2018-19 quadrivalent inactivated influenza vaccine treatment?

Research shows that quadrivalent influenza vaccines, which protect against four different flu virus strains, are effective in preventing flu-related complications and reducing healthcare use in young children. These vaccines are particularly useful when the flu virus strains predicted for the season do not match the circulating strains, offering broader protection than older trivalent vaccines. ^{1 2 3 4 5}

Is the quadrivalent inactivated influenza vaccine safe for humans?

The quadrivalent inactivated influenza vaccine has been shown to be safe in various studies, with no significant difference in adverse reactions compared to other influenza vaccines and no serious vaccine-related adverse events reported. ^{4 6 7 8 9}

How is the 2018-19 quadrivalent inactivated influenza vaccine different from other flu treatments?

The 2018-19 quadrivalent inactivated influenza vaccine is unique because it protects against four different flu viruses, including two types of influenza A and two types of influenza B, offering broader protection compared to the trivalent vaccine, which only covers three strains. ^{2 4 10 11 12}

What is the purpose of this trial?

Each winter, viruses belonging to two kinds of influenza A ("A/H1N1" \& "A/H3N2") and two kinds of influenza B ("B/Yamagata" \& "B/Victoria") can cause illness. Historically, the yearly influenza vaccine that was recommended in children was designed to protect against both kinds of influenza A but only one kind of influenza B. In a series of trials conducted between 2008-09 and 2010-11 (TITRE I, II, and IIB), the TITRE investigators measured antibody response to influenza B in children who were primed with two doses of trivalent inactivated influenza vaccine (TIV) containing B/Yamagata. Overall, the investigators found that 2 doses of vaccine containing B/Yamagata did not adequately prime children for response to the alternate B/Victoria antigen and that subsequent vaccine doses containing B/Victoria-lineage antigen strongly boosted antibodies to the B/Yamagata antigen that was introduced during first immunization priming, but with lower responses to B/Victoria. For the first time since 2009-10, the recommended B/Victoria component of the seasonal influenza vaccine has been changed, from B/Brisbane/60/2008 to B/Colorado/60/2007 for the coming 2018-19 season. The investigators thus have a unique opportunity to clarify lineage-specific influenza B responses in a well-characterized cohort of children originally primed to Yamagata. The investigators' main interest is to assess whether TITRE I children primed with two doses of B/Yamagata in 2008-09 have since or are now capable of achieving a sufficient antibody response to B/Victoria following a single dose of 2018-19 QIV, ten years after their initial TIV B/Yamagata priming exposure.

Research Team

Danuta M Skowronski, MD

Principal Investigator

BC Centre for Disease Control

Eligibility Criteria

This trial is for children in British Columbia or Quebec who participated in the TITRE I study and haven't had their 2018-19 flu shot. They should be generally healthy, able to complete the study, and have a parent/guardian fluent in English/French who can consent.

Inclusion Criteria

Child is healthy (stable chronic conditions acceptable) as established by health assessment interview and verbal history-directed health examination

My child can attend and complete all study procedures.

Parent or legal guardian is available and can be reached by phone during the study period

Exclusion Criteria

Child has a health condition which, in the opinion of the investigator, would interfere with the evaluation or pose a health risk to the child

My child hasn't had a live vaccine in the last 28 days and won't get one during the study.

The child has already gotten the flu shot for the 2018-19 flu season.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one dose of the 2018-19 quadrivalent inactivated influenza vaccine

1 day

1 visit (in-person)

Follow-up

Participants are monitored for seroprotection rate (SPR) for B/Victoria vaccine strains

4-6 weeks

1 visit (in-person)

Treatment Details

Interventions

• 2018-19 quadrivalent inactivated influenza vaccine

Trial Overview The trial tests if kids primed with B/Yamagata flu strain via vaccine years ago now respond well to B/Victoria strain in the updated quadrivalent influenza vaccine for the 2018-19 season.

Participant Groups

Group I: influenza vaccine recipients Experimental Treatment 1 Intervention

Participants of an earlier clinical trial (TITRE I) to receive one dose of the 2018-19 quadrivalent inactivated influenza vaccine

Who Is Running the Clinical Trial?

British Columbia Centre for Disease Control

Lead Sponsor

Trials

11

Recruited

2,600+

Vaccine Evaluation Center, Canada

Collaborator

Trials

3

Recruited

340+

Institut National en Santé Publique du Québec

Collaborator

Trials

10

Recruited

21,700+

McGill University Health Centre/Research Institute of the McGill University Health Centre

Collaborator

Trials

476

Recruited

170,000+

Findings from Research

The quadrivalent influenza vaccine AdimFlu-S showed strong immunogenicity in a study of 174 healthy children aged 3 to 17, achieving high seroprotection rates above 96.4% for all vaccine strains.

The vaccine was well tolerated with no serious adverse events reported over a 6-month follow-up period, indicating it is a safe option for improving protection against different influenza B lineages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in healthy subjects aged 3 to 17 years old: A phase III, open label, single-arm study. Chang, CY., Cho, CY., Lai, CC., et al.[2021]

The inactivated quadrivalent influenza vaccine (IIV4) demonstrated good immunogenicity, with seroconversion rates of over 60% for all four influenza strains tested, indicating it effectively stimulates the immune response in healthy individuals aged 3 years and older.

IIV4 was found to be non-inferior to the trivalent vaccine (IIV3) for the A strains and superior for the additional B strains, while showing no significant safety concerns, as no serious adverse events were reported and adverse reactions were similar across all groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of an inactivated quadrivalent influenza vaccine: A randomized, double-blind, controlled phase III study in healthy population aged ≥3 years. Chu, K., Xu, K., Tang, R., et al.[2022]

A study involving 102,911 participants in Australia found that the quadrivalent inactivated influenza vaccine had a low rate of adverse events, with no significant safety concerns identified across different age groups and vaccine brands.

Children aged 6 months to 4 years reported higher rates of adverse events (8.4%) compared to older individuals, but overall, the rates of fever and medical attendance remained low and within expected levels, suggesting the vaccine is safe for the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active surveillance of 2017 seasonal influenza vaccine safety: an observational cohort study of individuals aged 6 months and older in Australia. Pillsbury, AJ., Glover, C., Jacoby, P., et al.[2019]

The inactivated quadrivalent influenza vaccine (IIV4) was found to be safe and well-tolerated in a phase III trial involving 1,648 adults and 329 children/adolescents, with no serious adverse events reported.

IIV4 induced strong antibody responses to all four influenza strains it targets, meeting all immunogenicity criteria set by the European Medicines Agency, and showed comparable efficacy to the trivalent vaccine (IIV3) in both age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: A randomized, controlled, phase III trial. Cadorna-Carlos, JB., Nolan, T., Borja-Tabora, CF., et al.[2015]

The high-dose inactivated influenza vaccine quadrivalent (HD-IIV4) has been shown to be safe and effective in preventing influenza in adults aged 65 and older, with improved immunogenicity against additional B strains compared to standard vaccines.

Despite some increased adverse reactions like injection-site pain and myalgia, HD-IIV4 is recommended as the vaccine of choice for older adults due to its superior efficacy compared to other influenza vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Inactivated Influenza Vaccine Quadrivalent for Older Adults. Chahine, EB.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Impact of a quadrivalent inactivated influenza vaccine on influenza-associated complications and health care use in children aged 6 to 35 months: Analysis of data from a phase III trial in the Northern and Southern Hemispheres. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Correction to: Cell-Based Quadrivalent Inactivated Influenza Virus Vaccine (Flucelvax&#174; Tetra/Flucelvax Quadrivalent&#174;): A Review in the Prevention of Influenza. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Quadrivalent influenza vaccine in the United States. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in healthy subjects aged 3 to 17 years old: A phase III, open label, single-arm study. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of antibody response to 2018-19 cell-based vs. egg-based quadrivalent inactivated influenza vaccine in children. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a quadrivalent inactivated influenza vaccine compared to licensed trivalent inactivated influenza vaccines in adults. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Analysis of the adverse events following immunization with inactivated quadrivalent influenza vaccine from 2018 to 2020 in Zhejiang province, with a comparison to trivalent influenza vaccine. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of an inactivated quadrivalent influenza vaccine: A randomized, double-blind, controlled phase III study in healthy population aged ≥3 years. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Active surveillance of 2017 seasonal influenza vaccine safety: an observational cohort study of individuals aged 6 months and older in Australia. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Post-licensure surveillance of quadrivalent inactivated influenza (IIV4) vaccine in the United States, Vaccine Adverse Event Reporting System (VAERS), July 1, 2013-May 31, 2015. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: A randomized, controlled, phase III trial. [2015]

12. United States pubmed.ncbi.nlm.nih.gov

High-Dose Inactivated Influenza Vaccine Quadrivalent for Older Adults. [2021]