New Vaccine for Flu

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: GlaxoSmithKline

Must not be taking: Immune-modifying drugs, Corticosteroids

Disqualifiers: Malignancy, Immunodeficient, Neurological disorders, others

Compensation: Varies

Number of Visits: 5

996 Participants Needed

Trial Summary

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 immune-modifying drugs or have recently taken certain treatments like corticosteroids, you may need to stop them before joining the study. It's best to discuss your specific medications with the study team.

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

Research shows that mRNA vaccines can provide strong and long-lasting protection against influenza, even in very young and very old mice, and are effective in ferrets and pigs. These vaccines can quickly adapt to new strains, making them promising for preventing flu pandemics. ^{1 2 3 4 5}

Is the new mRNA flu vaccine generally safe for humans?

Research on mRNA vaccines, like those for COVID-19, shows they are generally safe, with some manageable side effects such as chills and fatigue. They have a lower risk of serious side effects compared to traditional flu vaccines. ^{6 7 8 9 10}

How does the mRNA Flu Vaccine differ from other flu treatments?

The mRNA Flu Vaccine is unique because it uses mRNA technology, which allows for rapid production and adaptation to new flu strains, offering potentially broader and longer-lasting protection compared to traditional flu vaccines. This vaccine targets multiple parts of the virus, including highly conserved proteins, which may provide cross-protection against different flu strains. ^{5 11 12 13 14}

What is the purpose of this trial?

The aim of this study is to evaluate the safety, reactogenicity and immunogenicity of the Flu Pandemic messenger RNA (mRNA) vaccine (including dose-finding and dose-confirmation) administered in healthy adults 18 to 85 years of age.

Eligibility Criteria

This trial is for healthy adults aged 18 to 85 who want to help test a new vaccine against the H5N1 influenza virus. Specific details about who can join are not provided, but typically participants must meet certain health standards and not have conditions that would exclude them.

Inclusion Criteria

Participants who can and will comply with the requirements of the protocol

Written informed consent obtained from the participant prior to any study-specific procedure

Body mass index (BMI) between 18 and 35 kg/m²

Exclusion Criteria

Pregnancy, lactation, or planning to become pregnant

Any other clinical condition that might pose additional risk to the participant

Medical conditions that preclude study participation or pose unacceptable risk

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive 2 doses of the investigational vaccine or placebo, 21 days apart, with safety data collected up to Day 29

4 weeks

2 visits (in-person)

Phase 2 Part A Treatment

Participants receive 2 doses of the investigational vaccine or placebo, 21 days apart, to assess immunogenicity, reactogenicity, and safety

4 weeks

2 visits (in-person)

Phase 2 Part B Treatment

Participants receive 1 dose of the investigational vaccine or placebo, with follow-up for safety and immunogenicity

26 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

26 weeks

Treatment Details

Interventions

• Flu Pandemic mRNA Vaccine

Trial Overview The study is testing different doses of an mRNA vaccine designed to protect against the H5N1 flu. Participants will receive one of several dose levels or a placebo, which does no harm but contains no active vaccine.

Participant Groups

Group I: Flu mRNA_Ph2_5_YA Part A Experimental Treatment 1 Intervention

YA participants receive 2 doses of Flu Pandemic mRNA_Dose level 5 during Phase 2 Part A, at Day 1 and at Day 22.

Group II: Flu mRNA_Ph2_5_OA Part A Experimental Treatment 1 Intervention

OA participants receive 2 doses of Flu Pandemic mRNA_Dose level 5 during Phase 2 Part A, at Day 1 and at Day 22.

Group III: Flu mRNA_Ph2_4_YA Part A Experimental Treatment 1 Intervention

YA participants receive 2 doses of Flu Pandemic mRNA_Dose level 4 during Phase 2 Part A, at Day 1 and at Day 22.

Group IV: Flu mRNA_Ph2_4_OA Part A Experimental Treatment 1 Intervention

OA participants receive 2 doses of Flu Pandemic mRNA_Dose level 4 during Phase 2 Part A, at Day 1 and at Day 22.

Group V: Flu mRNA_Ph2_3_YA Part A Experimental Treatment 1 Intervention

YA participants receive 2 doses of Flu Pandemic mRNA_Dose level 3 during Phase 2 Part A, at Day 1 and at Day 22.

Group VI: Flu mRNA_Ph2_3_OA Part A Experimental Treatment 1 Intervention

OA participants receive 2 doses of Flu Pandemic mRNA_Dose level 3 during Phase 2 Part A, at Day 1 and at Day 22.

Group VII: Flu mRNA_Ph2_2_YA Part A Experimental Treatment 1 Intervention

YA participants receive 2 doses of Flu Pandemic mRNA_Dose level 2 during Phase 2 Part A, at Day 1 and at Day 22.

Group VIII: Flu mRNA_Ph2_2_OA Part A Experimental Treatment 1 Intervention

OA participants receive 2 doses of Flu Pandemic mRNA_Dose level 2 during Phase 2 Part A, at Day 1 and at Day 22.

Group IX: Flu mRNA_Ph2_1_YA Part A Experimental Treatment 1 Intervention

YA participants receive 2 doses of Flu Pandemic mRNA_Dose level 1 during Phase 2 Part A, at Day 1 and at Day 22.

Group X: Flu mRNA_Ph2_1_OA Part A Experimental Treatment 1 Intervention

OA participants receive 2 doses of Flu Pandemic mRNA_Dose level 1 during Phase 2 Part A, at Day 1 and at Day 22.

Group XI: Flu mRNA_Ph2 Part B Experimental Treatment 1 Intervention

Participants receive 2 dose of Flu Pandemic mRNA dose level 6 in Phase 2 Part B, at Day 1 and at Day 22.

Group XII: Flu mRNA_Ph1_5_YA Experimental Treatment 1 Intervention

YA participants receive 2 doses of Flu Pandemic mRNA_Dose level 5 during Phase 1, at Day 1 and at Day 22.

Group XIII: Flu mRNA_Ph1_5_OA Experimental Treatment 1 Intervention

OA participants receive 2 doses of Flu Pandemic mRNA_Dose level 5 during Phase 1, at Day 1 and at Day 22.

Group XIV: Flu mRNA_Ph1_4_YA Experimental Treatment 1 Intervention

YA participants receive 2 doses of Flu Pandemic mRNA_Dose level 4 during Phase 1, at Day 1 and at Day 22.

Group XV: Flu mRNA_Ph1_4_OA Experimental Treatment 1 Intervention

OA participants receive 2 doses of Flu Pandemic mRNA_Dose level 4 during Phase 1, at Day 1 and at Day 22.

Group XVI: Flu mRNA_Ph1_3_YA Experimental Treatment 1 Intervention

YA participants receive 2 doses of Flu Pandemic mRNA_Dose level 3 during Phase 1, at Day 1 and at Day 22.

Group XVII: Flu mRNA_Ph1_3_OA Experimental Treatment 1 Intervention

OA participants receive 2 doses of Flu Pandemic mRNA_Dose level 3 during Phase 1, at Day 1 and at Day 22.

Group XVIII: Flu mRNA_Ph1_2_YA Experimental Treatment 1 Intervention

YA participants receive 2 doses of Flu Pandemic mRNA_Dose level 2 during Phase 1, at Day 1 and at Day 22.

Group XIX: Flu mRNA_Ph1_2_OA Experimental Treatment 1 Intervention

OA participants receive 2 doses of Flu Pandemic mRNA_Dose level 2 during Phase 1, at Day 1 and at Day 22.

Group XX: Flu mRNA_Ph1_1_YA Experimental Treatment 1 Intervention

YA participants receive 2 doses of Flu Pandemic mRNA_Dose level 1 during Phase 1, at Day 1 and at Day 22.

Group XXI: Flu mRNA_Ph1_1_OA Experimental Treatment 1 Intervention

OA participants receive 2 doses of Flu Pandemic mRNA_Dose level 1 during Phase 1, at Day 1 and at Day 22.

Group XXII: Influenza Virus Vaccine_Ph2 Part B Active Control 1 Intervention

Participants receive 2 doses of influenza virus vaccine administered in Phase 2 Part B, at Day 1 and at Day 22.

Group XXIII: Placebo_Ph1_YA Placebo Group 1 Intervention

YA participants receive 2 doses of Placebo during Phase 1, at Day 1 and at Day 22.

Group XXIV: Placebo_Ph2_YA Part A Placebo Group 1 Intervention

YA participants receive 2 doses of Placebo during Phase 2 Part A, at Day 1 and at Day 22.

Group XXV: Placebo_Ph1_OA Placebo Group 1 Intervention

OA Adult participants receive 2 doses of Placebo during Phase 1, at Day 1 and at Day 22.

Group XXVI: Placebo_Ph2_OA Part A Placebo Group 1 Intervention

OA participants receive 2 doses of Placebo during Phase 2 Part A, at Day 1 and at Day 22.

Group XXVII: Placebo_Ph2 Part B Placebo Group 1 Intervention

Participants receive 2 doses of Placebo during Phase 2 Part B, at Day 1 and at Day 22.

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

A novel mRNA vaccine targeting conserved proteins of the H1N1 influenza virus successfully induced broadly reactive T cells in both naïve and influenza-experienced ferrets, suggesting its potential effectiveness in diverse populations.

The booster vaccination significantly enhanced protection against a different strain of influenza (H7N9), indicating that this mRNA vaccine strategy could provide robust immunity against evolving influenza viruses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets. van de Ven, K., Lanfermeijer, J., van Dijken, H., et al.[2023]

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]

The study found that the pandemic influenza vaccine was highly effective, with a vaccination effectiveness of 74.2% in preventing hospitalization due to pandemic influenza among adults aged 18 and older, based on a multicenter analysis of 638 cases and 1250 controls.

In contrast, the seasonal influenza vaccine showed a much lower effectiveness of only 15.0%, highlighting the importance of prioritizing the pandemic vaccine during outbreaks to reduce hospitalizations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of pandemic and seasonal influenza vaccines in preventing pandemic influenza-associated hospitalization. Domínguez, A., Castilla, J., Godoy, P., et al.[2012]

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 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]

Both paper-based and web-based surveys reported similar rates of local and systemic adverse events following influenza vaccination, indicating that the method of data collection does not significantly affect the safety outcomes reported.

The paper-based survey, which recruited participants through general practitioners, was more representative of the elderly population targeted for influenza vaccination, suggesting that combining recruitment methods could enhance the accuracy of safety monitoring during mass vaccination campaigns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of different collection methods for reported adverse events following pandemic and seasonal influenza vaccination. Kemmeren, J., Honsbeek, M., Dijkstra, F., et al.[2017]

A rare case of delayed adverse events, including renal thrombosis and myocardial injury, occurred in a healthy adult female three months after receiving a booster shot of the Pfizer COVID-19 vaccine, highlighting the potential for serious side effects even after vaccination.

Despite the risks, the benefits of vaccination against COVID-19 are considered to outweigh the potential adverse events, emphasizing the need for ongoing monitoring and observation, particularly for individuals in specific risk categories.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The complexity of immunology: a rare adverse event following a Pfizer-BioNTech vaccine booster shot. Marigliano, B., Internullo, M., Scuro, L., et al.[2022]

A comparative safety study involving 18,755 individuals vaccinated with mRNA COVID-19 vaccines and 27,895 individuals vaccinated with influenza vaccines found that mRNA vaccines had a different safety profile, with more systemic reactions like chills and fatigue compared to the influenza vaccine.

While mRNA COVID-19 vaccines showed a higher risk for some manageable cardiovascular issues, such as hypertensive crisis and supraventricular tachycardia, they had a lower risk of serious neurological complications compared to influenza vaccines, indicating a generally favorable safety profile for mRNA vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative safety of mRNA COVID-19 vaccines to influenza vaccines: A pharmacovigilance analysis using WHO international database. Kim, MS., Jung, SY., Ahn, JG., et al.[2022]

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]

mRNA vaccine technology has rapidly advanced, leading to the first licensed vaccines for pandemics like SARS-CoV-2, demonstrating a fast development timeline of just a few months from antigen selection to clinical trials.

These vaccines are well tolerated and effective in animal models, showing promise for future vaccine development against various diseases by leveraging their simple composition and ability to adapt quickly to new pathogens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mRNA-Based Vaccines and Mode of Action. Gergen, J., Petsch, B.[2023]

The novel combined mRNA vaccine AR-CoV/IAV, which targets both COVID-19 and influenza A, successfully generated strong immune responses in mice, producing protective antibodies and cellular immunity against both viruses.

Immunization with AR-CoV/IAV effectively protected mice from severe outcomes associated with coinfection of influenza A and SARS-CoV-2 variants, demonstrating the potential of this vaccine platform for preventing respiratory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rational development of a combined mRNA vaccine against COVID-19 and influenza. Ye, Q., Wu, M., Zhou, C., et al.[2023]

Current influenza vaccines require regular updates and significant resources, limiting their effectiveness against viral outbreaks.

The mRNA vaccine platform, successfully used for SARS-CoV-2, shows promise for developing next-generation influenza vaccines, potentially leading to better immune responses and the possibility of a universal vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Message in a bottle: mRNA vaccination for influenza. Shartouny, JR., Lowen, AC.[2023]

Influenza A viruses pose a constant risk of zoonotic transmission to humans, with historical pandemics highlighting the potential severity of outbreaks, such as the 1918 pandemic that resulted in over 40 million deaths.

Despite advancements in vaccine development for (pre-)pandemic influenza, challenges remain due to the viruses' rapid evolution and diverse host range, necessitating ongoing research to improve vaccination strategies against future pandemic threats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avian Influenza A Virus Pandemic Preparedness and Vaccine Development. de Vries, RD., Herfst, S., Richard, M.[2020]

References

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

A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets. [2023]

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

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

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

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

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

Effectiveness of pandemic and seasonal influenza vaccines in preventing pandemic influenza-associated hospitalization. [2012]

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

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

6. 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]

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

Comparison of different collection methods for reported adverse events following pandemic and seasonal influenza vaccination. [2017]

8. Italy pubmed.ncbi.nlm.nih.gov

The complexity of immunology: a rare adverse event following a Pfizer-BioNTech vaccine booster shot. [2022]

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

Comparative safety of mRNA COVID-19 vaccines to influenza vaccines: A pharmacovigilance analysis using WHO international database. [2022]

10. 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]

11. Germany pubmed.ncbi.nlm.nih.gov

mRNA-Based Vaccines and Mode of Action. [2023]

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

Rational development of a combined mRNA vaccine against COVID-19 and influenza. [2023]

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

Message in a bottle: mRNA vaccination for influenza. [2023]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Avian Influenza A Virus Pandemic Preparedness and Vaccine Development. [2020]