mRNA Vaccine for Flu

Recruiting at 12 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sanofi

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

Disqualifiers: Immunodeficiency, Myocarditis, Guillain-Barré, others

Compensation: Varies

Number of Visits: 9

Duration: 3 weeks

240 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this phase 1/2 study is to investigate the safety and immunogenicity of different doses (high, medium and low) of a second generation structurally designed (SD2) H5 messenger ribonucleic acid (mRNA) vaccine against pandemic H5 influenza virus (pandemic flu H5 hemagglutinin (HA) mRNA SD2) in healthy younger and older adults. The study will aim to identify the appropriate dose for further clinical development of a potential pandemic response vaccine. The study duration per participant will be approximately 13 months. There will be two injections of placebo or pandemic flu H5 mRNA vaccine 21 days apart at high, medium and low doses. Study visits/contact include: 7 study visits and 1 telephone call. Vaccination visits (including blood samples) will occur at Day 01 and Day 22. Short-term follow-up visits (including blood samples) will occur 8 and 21 days after each injection. Participants will be also followed up (including blood samples) at 3 and 6 months after 2nd injection, and at 12 months after 2nd injection for safety.

Will I have to stop taking my current medications?

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 mRNA Vaccine for Flu treatment?

Research shows that mRNA vaccines can quickly and effectively produce strong immune responses against influenza, similar to their success with COVID-19 vaccines. In studies with animals, mRNA vaccines have provided protection against various strains of the flu, suggesting they could be a promising option for preventing flu infections. ^{1 2 3 4 5}

What safety data exists for the mRNA vaccine for flu?

The safety data for pandemic influenza vaccines, including those similar to the mRNA flu vaccine, show that adverse events are within the expected range for common flu vaccines. In a study of 507 vaccinated people, 20.3% experienced some complications, but severe cases were rare. ^{6 7 8 9 10}

How is the mRNA vaccine for flu different from other treatments?

The mRNA vaccine for flu is unique because it uses mRNA technology, which allows for rapid production and targets the hemagglutinin (HA) protein of the virus, potentially offering more consistent protection compared to traditional vaccines that can vary in effectiveness due to changes in the virus. This approach is inspired by the success of mRNA vaccines for COVID-19. ^{1 11 12 13 14}

Eligibility Criteria

This trial is for healthy adults aged 18 and older who can't get pregnant or agree to use contraception. Women of childbearing potential must test negative for pregnancy. It's not suitable for those unable to follow the study schedule.

Inclusion Criteria

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

I am a woman who can have children and have tested negative for pregnancy recently.

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 two injections of placebo or pandemic flu H5 mRNA vaccine 21 days apart at high, medium, and low doses

3 weeks

2 visits (in-person)

Short-term Follow-up

Short-term follow-up visits occur 8 and 21 days after each injection to monitor safety and immunogenicity

6 weeks

4 visits (in-person)

Long-term Follow-up

Participants are followed up at 3, 6, and 12 months after the second injection for safety and immunogenicity

12 months

3 visits (in-person), 1 call (virtual)

Treatment Details

Interventions

• Pandemic flu H5 HA mRNA SD2 vaccine

Trial Overview The trial tests a new mRNA vaccine against pandemic flu H5 strain at three different doses. Participants will receive two shots, 21 days apart, and be monitored over approximately 13 months with visits and blood samples.

Participant Groups

Group I: Group 3: Pandemic flu H5 HA mRNA SD2 vaccine (High dose) Experimental Treatment 1 Intervention

Participants will receive two injections of high dose pandemic flu H5 HA mRNA SD2 vaccine

Group II: Group 2: Pandemic flu H5 HA mRNA SD2 vaccine (Medium dose) Experimental Treatment 1 Intervention

Participants will receive two injections of medium dose pandemic flu H5 HA mRNA SD2 vaccine

Group III: Group 1: Pandemic flu H5 HA mRNA SD2 vaccine (Low dose) Experimental Treatment 1 Intervention

Participants will receive two injections of low dose pandemic flu H5 HA mRNA SD2 vaccine

Group IV: Placebo Placebo Group 1 Intervention

Participants will receive two injections of placebo

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

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]

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]

In a study of 507 vaccinated individuals, 20.3% experienced complications after receiving pandemic influenza vaccines, indicating that adverse events were more common than reported in spontaneous reporting systems.

The spontaneous reporting rate of adverse events was significantly lower (322-fold) than the rates identified through systematic follow-up, suggesting that formal observation studies may provide a more accurate assessment of vaccine safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events associated with pandemic influenza vaccines: comparison of the results of a follow-up study with those coming from spontaneous reporting. Carvajal, A., Ortega, PG., Sáinz, M., et al.[2010]

In a retrospective study of 66 individuals who received the H1N1 vaccine during a 2010 mass vaccination campaign in São Paulo, the most common adverse events reported were mild symptoms such as fever, headache, myalgia, and injection site pain.

Importantly, no serious adverse events were reported, indicating that the H1N1 vaccine was generally safe for those vaccinated at this center.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spontaneous reporting of adverse events following pandemic influenza A (H1N1) immunization in a reference center in the State of São Paulo, Brazil. Oliveira, DS., Lara, AN., Luiz, AM., et al.[2022]

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

Targeting the HA2 subunit of influenza A virus hemagglutinin via CD40L provides universal protection against diverse subtypes. [2023]

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

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Adenoviral-Vectored Centralized Consensus Hemagglutinin Vaccine Provides Broad Protection against H2 Influenza a Virus. [2022]

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

Beta-defensin 2 enhances immunogenicity and protection of an adenovirus-based H5N1 influenza vaccine at an early time. [2021]

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

Adverse events associated with pandemic influenza vaccines: comparison of the results of a follow-up study with those coming from spontaneous reporting. [2010]

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

Safety, Tolerability and Immunogenicity of an MF59-adjuvanted, Cell Culture-derived, A/H5N1, Subunit Influenza Virus Vaccine: Results From a Dose-finding Clinical Trial in Healthy Pediatric Subjects. [2020]

8. Spain pubmed.ncbi.nlm.nih.gov

[Variability in the reporting of adverse reactions to the pandemic and seasonal influenza vaccine: seasons 2009-2010 and 2010-2011. Valencian community, Spain]. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of adjuvanted inactivated split-virion and whole-virion influenza A (H5N1) vaccines in children: a phase I-II randomized trial. [2010]

10. Brazil pubmed.ncbi.nlm.nih.gov

Spontaneous reporting of adverse events following pandemic influenza A (H1N1) immunization in a reference center in the State of São Paulo, Brazil. [2022]

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

Influenza A viruses: why focusing on M2e-based universal vaccines. [2021]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Characterization of humoral and cell-mediated immunity induced by mRNA vaccines expressing influenza hemagglutinin stem and nucleoprotein in mice and nonhuman primates. [2022]

13. England pubmed.ncbi.nlm.nih.gov

An H5N1 M2e-based multiple antigenic peptide vaccine confers heterosubtypic protection from lethal infection with pandemic 2009 H1N1 virus. [2021]

14. England pubmed.ncbi.nlm.nih.gov

GSK's novel split-virus adjuvanted vaccines for the prevention of the H5N1 strain of avian influenza infection. [2011]