mRNA Vaccine for Flu

Recruiting at 17 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 45

Duration: 3 weeks

276 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate a pandemic flu H5 strain messenger ribonucleic acid (mRNA) vaccine at 3 dose levels (low, medium, and high) in comparison with placebo in 276 healthy adult participants to select the adequate dose for further clinical development. The duration per participant will be approximately 13 months.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy, long-term systemic corticosteroids, or anticoagulants, you may not be eligible. It's best to discuss your specific medications with the trial investigator.

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, long-term corticosteroids, or anticoagulants, you may not be eligible to participate.

What data supports the idea that mRNA Vaccine for Flu is an effective treatment?

The available research shows that mRNA vaccines for flu, specifically those targeting the H5N1 strain, are effective in generating a strong immune response. Clinical studies have found that two doses of the vaccine are generally needed to achieve the desired level of immunity. The use of adjuvants, which are substances that enhance the body's immune response to the vaccine, allows for less of the vaccine to be used while still being effective. Additionally, these vaccines can provide cross-protection against different strains of the virus. Compared to other treatments, the mRNA vaccine with adjuvants has shown to boost immunity more effectively, as seen in studies with ferrets where it reduced viral presence and lung damage. This suggests that the mRNA vaccine is a promising option for flu prevention. ^{1 2 3 4 5}

What data supports the effectiveness of the mRNA Vaccine for Flu treatment?

Research shows that H5N1 vaccines, especially when combined with adjuvants (substances that enhance the body's immune response), can produce strong immune responses and offer cross-protection against different virus strains. Studies also indicate that adjuvanted vaccines can boost immunity and provide better protection, as seen in trials with other influenza vaccines. ^{1 2 3 4 5}

What safety data is available for the mRNA flu vaccine?

The safety data for the mRNA flu vaccine, including variants like the H5N1 vaccine, shows that it is generally well-tolerated across different age groups. Studies on vaccines such as Aflunov, an adjuvanted H5N1 vaccine, indicate it is safe and well-tolerated in infants, children, adolescents, adults, and the elderly. Clinical trials, including a phase III trial with 5071 adults, reported that the vaccine's safety and reactogenicity profile is clinically acceptable, with pain being the most common adverse event. Other studies confirm that the vaccine is safe and immunogenic, with minimal adverse events like injection site pain, malaise, and fever. Overall, the vaccine meets safety criteria for pandemic influenza vaccines. ^{5 6 7 8 9}

Is the mRNA vaccine for flu safe for humans?

The mRNA vaccine for flu, evaluated under various names like Aflunov and others, has been shown to be safe in humans. Clinical studies have found it to be well-tolerated in different age groups, with common side effects being mild, such as pain at the injection site. Serious adverse events were rare, making the vaccine's safety profile acceptable for use against pandemic influenza. ^{5 6 7 8 9}

Is the mRNA Vaccine for Flu a promising treatment?

Yes, the mRNA Vaccine for Flu is promising because it can quickly provide protection against the H5N1 flu virus, which could cause a pandemic. It can be given before a pandemic starts to prepare people and help them build strong immunity. The vaccine has shown to be safe and effective in creating a strong immune response, even against different strains of the virus. ^{1 5 6 10 11}

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

The mRNA vaccine for flu is unique because it uses a genetic approach to stimulate the immune system, potentially offering cross-protective and long-lasting responses against various strains of the H5N1 virus. Unlike traditional vaccines, it can be administered quickly in the event of a pandemic, and its effectiveness can be enhanced with adjuvants, which are substances that boost the body's immune response to the vaccine. ^{1 5 6 10 11}

Eligibility Criteria

This clinical trial is open to healthy adults aged 18 and older who are interested in testing a new pandemic flu H5 mRNA vaccine. The study aims to find the right dose for further research. Participants will be involved for about 13 months.

Inclusion Criteria

I am 18 years old or older.

I am not pregnant or breastfeeding and either cannot have children or will use birth control.

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

Exclusion Criteria

I have a weak immune system or have been on long-term steroids.

Chronic illness that might interfere with study conduct or completion

I do not have a severe illness or fever today.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 injections of pandemic flu H5 mRNA vaccine or placebo 21 days apart

3 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and antibody titers

12 months

Multiple visits (in-person and virtual) at Day 43, Day 112, and Day 202

Treatment Details

Interventions

• Pandemic flu H5 mRNA vaccine

Trial Overview The trial is testing three different doses of a new pandemic flu H5 mRNA vaccine against a placebo, which has no active ingredients. It's designed to see how safe the vaccine is and how well it triggers an immune response.

Participant Groups

Group I: Group 3: High Dose Pandemic flu H5 mRNA vaccine Experimental Treatment 1 Intervention

Participants will receive 2 injections of pandemic flu H5 mRNA vaccine 21 days apart (at Day 01 and Day 22)

Group II: Group 2: Medium Dose Pandemic flu H5 mRNA vaccine Experimental Treatment 1 Intervention

Participants will receive 2 injections of pandemic flu H5 mRNA vaccine 21 days apart (at Day 01 and Day 22)

Group III: Group 1: Low Dose Pandemic flu H5 mRNA vaccine Experimental Treatment 1 Intervention

Participants will receive 2 injections of pandemic flu H5 mRNA vaccine 21 days apart (at Day 01 and Day 22)

Group IV: Group 4: Placebo Placebo Group 1 Intervention

Participants will receive 2 injections of placebo 21 days apart (at Day 01 and Day 22)

Pandemic flu H5 mRNA vaccine is already approved in United States, European Union for the following indications:

Approved in United States as Audenz for:

• Prevention of disease caused by influenza A (H5N1) virus

Approved in European Union as Aflunov for:

• Prevention of influenza A (H5N1) virus infection

Approved in European Union as Adjupanrix for:

• Prevention of influenza A (H5N1) virus infection

Approved in European Union as Foclivia for:

• Prevention of influenza A (H5N1) virus infection

Approved in European Union as Pumarix for:

• Prevention of influenza A (H5N1) virus infection

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

Vaccines for the H5N1 influenza virus are being developed to use less antigen and induce long-lasting immunity, which is crucial for rapid response during a pandemic, as shown by clinical studies requiring two doses for adequate immunity.

The inclusion of oil-in-water adjuvants allows for lower antigen doses while still achieving necessary immune responses, and prime-boost strategies can enhance the effectiveness of the vaccine by eliciting stronger immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

H5N1 vaccines in humans. Baz, M., Luke, CJ., Cheng, X., et al.[2021]

In a study of 60 kidney transplant recipients, only 34.5% developed a protective immune response to the Pandemrix® H1N1 vaccine, compared to 91% of healthy controls, indicating a significantly reduced efficacy in this vulnerable population.

After a booster vaccination, only 42% of 19 patients achieved a protective antibody level, and 5.6% of the 107 reviewed patients developed new donor-specific HLA antibodies, suggesting potential safety concerns with the vaccine in transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune response to an adjuvanted influenza A H1N1 vaccine (Pandemrix(®)) in renal transplant recipients. Brakemeier, S., Schweiger, B., Lachmann, N., et al.[2012]

The AS03-adjuvanted H1N1 vaccine (Pandemrix) was found to have a clinically acceptable safety profile, with adverse events primarily consistent with seasonal illnesses, in a cohort of 9143 individuals followed for 6 months after vaccination.

While some medically attended adverse events (MAEs) and serious adverse events (SAEs) were reported, the overall incidence was low, and the number of deaths observed post-vaccination was fewer than expected, indicating the vaccine's safety across all age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of AS03-adjuvanted split-virion H1N1 (2009) pandemic influenza vaccine: a prospective cohort study. Nazareth, I., Tavares, F., Rosillon, D., et al.[2021]

Heterologous vaccination with an AS03-adjuvanted seasonal trivalent and pandemic H5N1 vaccine provided partial protection against the H1N1 virus in influenza-naïve ferrets, indicating the potential effectiveness of this vaccination strategy during a pandemic.

The AS03-adjuvanted pandemic H1N1 vaccine significantly enhanced antibody responses and reduced viral shedding and lung damage compared to non-adjuvanted vaccines, highlighting the importance of using adjuvanted vaccines for better protection against influenza in unprimed individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pandemic H1N1 vaccine requires the use of an adjuvant to protect against challenge in naïve ferrets. Baras, B., de Waal, L., Stittelaar, KJ., et al.[2011]

The MF59-adjuvanted A/H5N1 pre-pandemic vaccine demonstrated strong immunogenicity, achieving a seroconversion rate of 56% in adults and meeting European licensure criteria, indicating it can effectively stimulate an immune response against the virus.

The vaccine was well tolerated, showing lower reactogenicity compared to the seasonal influenza vaccine, making it a suitable option for pre-pandemic vaccination in both adults and the elderly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of an MF59(®)-adjuvanted A/H5N1 pre-pandemic influenza vaccine in adults and the elderly. Vesikari, T., Forstén, A., Herbinger, KH., et al.[2022]

Aflunov(®), a prepandemic monovalent A/H5N1 influenza vaccine, has been shown to be safe and well-tolerated across various age groups, including infants and the elderly, with no observed maternal or embryo-fetal toxicity in nonclinical studies.

The vaccine demonstrated strong immunogenicity against both related and different strains of the H5N1 virus, suggesting it could effectively prepare the immune system for potential future pandemics caused by this virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflunov(®): a prepandemic influenza vaccine. Gasparini, R., Amicizia, D., Lai, PL., et al.[2013]

In a phase III clinical trial involving 5071 healthy adults, the AS-H5N1 vaccine showed a clinically acceptable safety and reactogenicity profile, with less than 1% of participants withdrawing due to adverse events.

While more participants in the AS-H5N1 group reported general or local adverse events compared to those receiving the licensed seasonal influenza vaccine, no serious adverse events related to vaccination were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and reactogenicity profile of an adjuvanted H5N1 pandemic candidate vaccine in adults within a phase III safety trial. Rümke, HC., Bayas, JM., de Juanes, JR., et al.[2021]

The study demonstrated that the aluminium hydroxide adjuvanted H5N1 vaccine was well tolerated and safe for children aged 6 months to 17 years, with no significant adverse effects reported during the 21-day follow-up period.

The vaccine showed higher immunogenicity in children when using the 30 microg HA with adjuvant formulation compared to the 7.5 microg HA without adjuvant, indicating that the adjuvant significantly enhances the immune response against the H5N1 virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, humoral and cell mediated immune responses to two formulations of an inactivated, split-virion influenza A/H5N1 vaccine in children. Chotpitayasunondh, T., Thisyakorn, U., Pancharoen, C., et al.[2021]

The study involved 480 adult and elderly volunteers who received varying doses of a whole-virion, inactivated, adjuvanted H5N1 vaccine, demonstrating that a single dose of 6 micrograms or more met safety and immunogenicity standards for pandemic vaccines.

The vaccine was found to be safe, with only mild side effects like injection site pain and fever, and it effectively triggered immune responses with low doses, requiring only one injection, which is a significant advantage over other H5N1 vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single-dose influenza A (H5N1) vaccine safe and immunogenic in adult and elderly patients: an approach to pandemic vaccine development. Vajo, Z., Wood, J., Kosa, L., et al.[2021]

The Toll-like receptor 3 agonist, Ampligen, has been shown to be safe in humans and acts as an effective mucosal adjuvant for intranasal H5N1 influenza vaccines, enhancing immune response.

Intranasal vaccination with Ampligen-adjuvanted H5N1 vaccine not only produced specific antibodies in the nasal mucosa and serum but also provided protection against both closely related and different strains of the virus in mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PolyI:polyC12U adjuvant-combined intranasal vaccine protects mice against highly pathogenic H5N1 influenza virus variants. Ichinohe, T., Ainai, A., Tashiro, M., et al.[2017]

The emergence of the highly pathogenic avian influenza A(H5N1) virus since 1997 raises concerns about a potential human pandemic, prompting discussions on pre-pandemic vaccination strategies.

Recent advancements in effective adjuvants have led to the approval of a vaccine for human use in the EU, suggesting that it is feasible to provide basic immunity against H5N1, although logistical challenges remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Registration of the first human vaccine against the highly pathogenic avian influenza A(H5N1) virus: considerations]. de Jong, JC., Osterhaus, AD.[2008]

References

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

H5N1 vaccines in humans. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Immune response to an adjuvanted influenza A H1N1 vaccine (Pandemrix(®)) in renal transplant recipients. [2012]

3. England pubmed.ncbi.nlm.nih.gov

Safety of AS03-adjuvanted split-virion H1N1 (2009) pandemic influenza vaccine: a prospective cohort study. [2021]

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

Pandemic H1N1 vaccine requires the use of an adjuvant to protect against challenge in naïve ferrets. [2011]

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

Safety and immunogenicity of an MF59(®)-adjuvanted A/H5N1 pre-pandemic influenza vaccine in adults and the elderly. [2022]

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

Aflunov(®): a prepandemic influenza vaccine. [2013]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and reactogenicity profile of an adjuvanted H5N1 pandemic candidate vaccine in adults within a phase III safety trial. [2021]

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

Safety, humoral and cell mediated immune responses to two formulations of an inactivated, split-virion influenza A/H5N1 vaccine in children. [2021]

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

A single-dose influenza A (H5N1) vaccine safe and immunogenic in adult and elderly patients: an approach to pandemic vaccine development. [2021]

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

PolyI:polyC12U adjuvant-combined intranasal vaccine protects mice against highly pathogenic H5N1 influenza virus variants. [2017]

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

[Registration of the first human vaccine against the highly pathogenic avian influenza A(H5N1) virus: considerations]. [2008]