Flu Vaccine for Influenza

Recruiting at 23 trial locations

Overseen By Trial Transparency email recommended (Toll free for US & Canada)

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sanofi Pasteur, a Sanofi Company

Must not be taking: Immunosuppressants, Corticosteroids, Anticoagulants, others

Disqualifiers: Immunodeficiency, Myocarditis, Guillain-Barré, others

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

Compensation: Varies

Number of Visits: 4

Duration: 1 day

1158 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and immunogenicity of a single intramuscular injection of different formulations of a hexavalent influenza messenger ribonucleic acid (mRNA) vaccine composed of differing dose levels of trivalent (TIV) mRNA hemagglutinin (HA) in combination with TIV mRNA-neuraminidase (NA) compared to an active control ((Fluzone standard-dose quadrivalent influenza vaccine (QIV-SD) or Fluzone high-dose quadrivalent influenza vaccine (QIV-HD) in adults 50 years of age and older.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or long-term systemic corticosteroids, you may not be eligible to participate.

What data supports the effectiveness of the Hexavalent Influenza mRNA Vaccine treatment?

Research on similar mRNA vaccines shows they can produce strong immune responses and protect against various strains of the flu virus. For example, a quadrivalent mRNA vaccine was effective in mice, providing full protection against flu symptoms and death, even at low doses. ^{1 2 3 4 5}

Is the influenza vaccine generally safe for humans?

The influenza vaccine is generally considered safe, but like any vaccine, it can have side effects. Most side effects are mild, such as soreness at the injection site or mild fever. Rarely, more serious reactions can occur, such as Guillain-Barré syndrome (a rare nerve disorder) or oculorespiratory syndrome (a condition affecting the eyes and breathing). ^{6 7 8 9 10}

How does the Hexavalent Influenza mRNA Vaccine differ from other flu treatments?

The Hexavalent Influenza mRNA Vaccine is unique because it uses mRNA technology to quickly produce vaccines that can target multiple strains of the flu virus, potentially offering broader protection compared to traditional flu vaccines that are often less effective due to changes in the virus. This approach is inspired by the success of mRNA vaccines for COVID-19 and allows for rapid adaptation to new flu strains. ^{1 2 11 12 13}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

This trial is for adults aged 50 or older who are in good health. Women must be postmenopausal, surgically sterile, or willing to use effective contraception. Participants need a negative pregnancy test before receiving the study vaccine.

Inclusion Criteria

I agree to use effective birth control or abstain from sex starting 4 weeks before until 12 weeks after the treatment.

I am 50 years old or older.

I am not able to have children because I am postmenopausal or have been surgically sterilized.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intramuscular injection of the hexavalent influenza mRNA vaccine or active control

1 day

1 visit (in-person) on Day 01

Follow-up

Participants are monitored for safety and immunogenicity, including solicited and unsolicited adverse events, and antibody titers

12 months

Visits on Day 03, Day 09, Day 29, Day 181, and a telephone call on Day 366

Treatment Details

Interventions

• Hexavalent Influenza mRNA Vaccine

Trial Overview The study tests different formulations of a hexavalent influenza mRNA vaccine against standard and high-dose quadrivalent flu vaccines. It measures safety and immune response after one intramuscular injection in participants.

Participant Groups

Group I: Group 9 - TIV mRNA-HA Vaccine 2 Experimental Treatment 1 Intervention

Participants will receive single dose of TIV mRNA-HA Vaccine 2

Group II: Group 8 - TIV mRNA-NA Experimental Treatment 1 Intervention

Participants will receive a single dose of TIV mRNA-NA

Group III: Group 7 - TIV mRNA-HA Vaccine 1 Experimental Treatment 1 Intervention

Participants will receive a single dose of TIV mRNA-HA Vaccine 1

Group IV: Group 6 - Hexavalent (Combination 6) Experimental Treatment 2 Interventions

Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 6)

Group V: Group 5 - Hexavalent (Combination 5) Experimental Treatment 2 Interventions

Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 5)

Group VI: Group 4 - Hexavalent (Combination 4) Experimental Treatment 2 Interventions

Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 4)

Group VII: Group 3 - Hexavalent (Combination 3) Experimental Treatment 2 Interventions

Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 3)

Group VIII: Group 2 - Hexavalent (Combination 2) Experimental Treatment 2 Interventions

Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 2)

Group IX: Group 1 - Hexavalent (Combination 1) Experimental Treatment 2 Interventions

Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 1)

Group X: Group 10 - QIV-SD Active Control 1 Intervention

Participants will receive single dose of QIV-SD vaccine (for participants 50 to 64 years of age only)

Group XI: Group 11 - QIV-HD Active Control 1 Intervention

Participants will receive single dose of QIV-HD vaccine

Who Is Running the Clinical Trial?

Sanofi Pasteur, a Sanofi Company

Lead Sponsor

Trials

429

Recruited

6,140,000+

Paul Hudson

Sanofi Pasteur, a Sanofi Company

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Dr. Thomas Triomphe

Sanofi Pasteur, a Sanofi Company

Chief Medical Officer since 2020

MD from Tehran University of Medical Sciences

Findings from Research

A quadrivalent mRNA vaccine targeting four seasonal influenza virus strains was shown to induce strong antibody responses in mice, with effective protection against illness even at low doses (as low as 1 μg per antigen).

The mRNA vaccine demonstrated the ability to prevent weight loss and protect against morbidity and mortality from influenza, highlighting its potential as a promising alternative to traditional influenza vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seasonal quadrivalent mRNA vaccine prevents and mitigates influenza infection. Kackos, CM., DeBeauchamp, J., Davitt, CJH., et al.[2023]

The newly developed mRNA-lipid nanoparticle vaccine targets all 20 known influenza A virus subtypes and influenza B virus lineages, showing promise in eliciting strong immune responses in mice and ferrets.

This multivalent vaccine not only produced high levels of cross-reactive antibodies but also provided protection against both matched and mismatched viral strains, suggesting its potential effectiveness against diverse influenza viruses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. Arevalo, CP., Bolton, MJ., Le Sage, V., et al.[2023]

Annual influenza vaccination is the largest vaccination effort in the USA, with ongoing discussions about moving towards universal vaccination strategies.

While there is substantial safety data, rare serious adverse events, such as Guillain-Barré syndrome linked to the 1976-1977 vaccine and oculorespiratory syndrome in Canada, highlight the need for continuous monitoring of vaccine safety, especially during pandemic situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring the safety of annual and pandemic influenza vaccines: lessons from the US experience. Iskander, J., Broder, K.[2008]

In a study of 98 elderly individuals in Brazil, 84.7% of reported post-vaccination events were classified as non-severe, with local reactions being the most common (64.3%).

The findings highlight the importance of providing targeted information to healthcare providers to ensure safe vaccination practices and minimize avoidable adverse events in the elderly population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse events following immunization against influenza the in elderly in Brazil]. Rodrigues, D., de Marchi Bacellos de Dalri, RC.[2023]

The quadrivalent mRNA-1010 vaccine demonstrated strong humoral immunogenicity, eliciting higher hemagglutination inhibition (HAI) titers against influenza A strains compared to a standard inactivated vaccine, indicating its potential effectiveness in preventing influenza.

No significant safety concerns were reported during the trial, although mild adverse reactions were more common with mRNA-1010, suggesting it is generally safe for use in healthy adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis. Lee, IT., Nachbagauer, R., Ensz, D., et al.[2023]

mRNA vaccines for influenza have been shown to induce strong and long-lasting immunity in both very young and very old mice, demonstrating their potential effectiveness across age groups.

These vaccines not only provide protection against influenza A virus but also target multiple viral antigens, suggesting they could serve as cross-protective vaccines, similar in efficacy to licensed vaccines in larger animals like pigs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Petsch, B., Schnee, M., Vogel, AB., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Seasonal quadrivalent mRNA vaccine prevents and mitigates influenza infection. [2023]

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

A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. [2023]

3. Canada pubmed.ncbi.nlm.nih.gov

Repeated influenza vaccination for preventing severe and fatal influenza infection in older adults: a multicentre case-control study. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Inactivated trivalent influenza vaccination is associated with lower mortality among patients with COVID-19 in Brazil. [2023]

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

High-dose trivalent influenza vaccine compared to standard dose vaccine in elderly adults: safety, immunogenicity and relative efficacy during the 2009-2010 season. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Monitoring the safety of annual and pandemic influenza vaccines: lessons from the US experience. [2008]

7. Canada pubmed.ncbi.nlm.nih.gov

Assessing vaccine safety within Ontario's Universal Influenza Immunization Program, 2012-2013 to 2014-2015. [2022]

8. Colombia pubmed.ncbi.nlm.nih.gov

[Adverse events following immunization against influenza the in elderly in Brazil]. [2023]

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

Side effects associated with influenza vaccination in healthy working adults. A randomized, placebo-controlled trial. [2006]

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

Frequency of adverse reactions after influenza vaccination. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis. [2023]

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

Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. [2021]