mRNA-1010 Vaccine for Flu

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: ModernaTX, Inc.

Must not be taking: Immunosuppressants, Immunoglobulins

Disqualifiers: Immunodeficiency, Severe infections, Anaphylaxis, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new flu vaccine called mRNA-1010 to see if it is safe and effective for people who need flu shots. The new vaccine uses a small piece of genetic material to help the body recognize and fight the flu virus.

Do I need to stop 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 systemic immunosuppressants or certain immune therapies, you may need to stop them before joining the trial. It's best to discuss your specific medications with the trial team.

Is the mRNA-1010 vaccine for flu generally safe for humans?

Research on similar vaccines, like those for influenza and COVID-19, shows that most adverse events (unwanted effects) are known, non-serious, and occur shortly after vaccination. There have been no strong signals of unknown or serious adverse events in studies from Brazil and Denmark. ^{1 2 3 4 5}

How is the mRNA-1010 vaccine different from other flu vaccines?

The mRNA-1010 vaccine is unique because it uses messenger RNA (mRNA) technology to stimulate an immune response against the flu, potentially offering a faster and more adaptable production process compared to traditional flu vaccines. It has shown to elicit higher immune responses for certain flu strains and is designed to be a quadrivalent vaccine, targeting multiple strains of the virus. ^{6 7 8 9 10}

Research Team

Eligibility Criteria

This trial is for healthy adults who can become pregnant but are not currently, using contraception or abstaining from pregnancy-causing activities. They must have a BMI of 18-<40 kg/m^2 (Part A only), no acute illness/fever before vaccination, and no history of severe allergies to mRNA or flu vaccines.

Inclusion Criteria

I am not pregnant, not breastfeeding, and will use birth control during and after the vaccine trial.

In Part A of the study, your BMI needs to be between 18 and less than 40. There is no BMI requirement for Part B.

Exclusion Criteria

You had a serious allergic reaction in the past after getting an mRNA or flu vaccine, or any of the ingredients in those vaccines, like egg protein.

I have used strong immune system suppressants for more than 2 weeks in the last 6 months.

Acutely ill or febrile (temperature ≥ 38.0°Celsius (C)/100.4° Fahrenheit (F) hours before or at the D1 vaccination visit. Participants meeting this criterion may be rescheduled within the 28-day screening window.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of the assigned vaccine by intramuscular injection on Day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and immunogenicity, with seroresponse measured at Day 29

4 weeks

1 visit (in-person)

Extended Follow-up

Participants are monitored for long-term immunogenicity with seroresponse measured at Days 57, 121, and 181

6 months

3 visits (in-person)

Treatment Details

Interventions

• Adjuvanted Quadrivalent Influenza Vaccine (Virus Therapy)
• Egg-based Quadrivalent Influenza Vaccine (Virus Therapy)
• Inactivated Influenza Vaccine (Virus Therapy)
• mRNA-1010 (Virus Therapy)

Trial Overview The study tests the safety and immune response effectiveness of mRNA-1010 compared to other flu vaccines. Participants will be assessed on Day 29 for their body's defense against specific influenza strains.

Participant Groups

Group I: Parts A and B - Arm 5: mRNA-1010 (Age Group 65-80 years) Experimental Treatment 1 Intervention

Participants will receive a single dose of mRNA-1010 by IM injection on Day 1.

Group II: Parts A and B - Arm 1: mRNA-1010 (Age Group 18-50 years) Experimental Treatment 1 Intervention

Participants will receive a single dose of mRNA-1010 by intramuscular (IM) injection on Day 1.

Group III: Part C - Arm 3: mRNA-1045 (Age Group 18-50 years) Experimental Treatment 1 Intervention

Participants will receive a single dose of mRNA-1045 by IM injection on Day 1.

Group IV: Part C - Arm 2: mRNA-1010 and mRNA-1345 (Age Group 18-50 years) Experimental Treatment 2 Interventions

Participants will receive one dose of mRNA-1010 at Day 1 followed by one dose of mRNA-1345 in the contralateral arm at Day 29.

Group V: Part C - Arm 1: mRNA-1010 and mRNA-1345 (Age Group 18-50 years) Experimental Treatment 2 Interventions

Participants will receive one dose of mRNA-1010 concomitantly injected with one dose of mRNA-1345 in the contralateral arm at Day 1.

Group VI: Parts A and B - Arm 2: Egg-based Quadrivalent Influenza Vaccine (Age Group 18-50 years) Active Control 1 Intervention

Participants will receive a single dose of egg-based quadrivalent influenza vaccine by IM injection on Day 1.

Group VII: Parts A and B - Arm 3: Adjuvanted Quadrivalent Influenza Vaccine (Age Group 65-80 years) Active Control 1 Intervention

Participants will receive a single dose of adjuvanted quadrivalent influenza vaccine by IM injection on Day 1.

Group VIII: Parts A and B - Arm 4: Inactivated Influenza Vaccine (Age Group 65-80 years) Active Control 1 Intervention

Participants will receive a single dose of inactivated influenza vaccine by IM injection on Day 1.

Who Is Running the Clinical Trial?

ModernaTX, Inc.

Lead Sponsor

Trials

127

Recruited

66,790,000+

Dr. Stephen Hoge

ModernaTX, Inc.

Chief Medical Officer

MD from Harvard Medical School

Stéphane Bancel

ModernaTX, Inc.

Chief Executive Officer since 2011

MBA from Harvard Business School, MSc in Engineering from École Centrale Paris

Findings from Research

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]

During the 2009-2010 influenza A/H1N1v vaccination campaign in Denmark, 607 reports of adverse events were submitted, primarily involving non-serious reactions occurring within one day of vaccination, indicating a relatively low risk of serious side effects.

The study found no strong signals for unknown or serious adverse events linked to the vaccine, highlighting the safety of the influenza A/H1N1v vaccination during this period, although it also pointed out the limitations of relying solely on spontaneous reporting for assessing vaccine safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spontaneous reporting of adverse events following immunisation against pandemic influenza in Denmark November 2009-March 2010. Folkenberg, M., Callréus, T., Svanström, H., et al.[2011]

Cardiac complications, particularly myopericarditis, were the most frequently reported severe adverse events associated with mRNA COVID-19 vaccines, with systemic reactions being more common after the second dose.

Despite the higher number of reported adverse effects following the Pfizer vaccine, the review concluded that the overall benefits of mRNA vaccines in controlling the COVID-19 pandemic significantly outweigh the risks of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Adverse Events Related to COVID-19 mRNA Vaccines; a Systematic Review. SeyedAlinaghi, S., Karimi, A., Pashaei, Z., 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]

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]

The mRNA-lipid nanoparticle vaccine has been shown to provide protection against 20 different lineages of the influenza virus, indicating its broad efficacy.

This innovative vaccine approach utilizes lipid nanoparticles to deliver mRNA, which instructs cells to produce viral proteins, prompting an immune response that can recognize and combat multiple influenza strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influenza universe in an mRNA vaccine. Kelvin, AA., Falzarano, D.[2023]

The mRNA vaccines for H10N8 and H7N9 influenza viruses were found to be safe and well-tolerated, with no serious adverse events reported in the trials involving 201 participants for H10N8 and 156 participants for H7N9.

Both vaccines elicited strong humoral immune responses, with the 100-µg dose of H10N8 achieving 100% of participants with protective antibody levels, and the 50-µg dose of H7N9 achieving 100% seroconversion in neutralization tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. Feldman, RA., Fuhr, R., Smolenov, I., et al.[2020]

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]

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]

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. Colombia pubmed.ncbi.nlm.nih.gov

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

2. Netherlands pubmed.ncbi.nlm.nih.gov

Spontaneous reporting of adverse events following immunisation against pandemic influenza in Denmark November 2009-March 2010. [2011]

3. Iran pubmed.ncbi.nlm.nih.gov

Safety and Adverse Events Related to COVID-19 mRNA Vaccines; a Systematic Review. [2022]

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

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

5. 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]

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

The influenza universe in an mRNA vaccine. [2023]

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

mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. [2020]

8. 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]

9. 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]

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

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