Flu Vaccine for Influenza

Recruiting at 19 trial locations

Overseen By Jeffrey McGuckin, MHS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Biomedical Advanced Research and Development Authority

Must not be taking: Glucocorticoids, Anticancer chemotherapy

Disqualifiers: HIV, Hepatitis B/C, Schizophrenia, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

1380 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain conditions like long-term use of high-dose steroids or recent vaccination may affect eligibility, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the A/H5 Influenza Vaccine treatment?

Research shows that using adjuvants (substances that enhance the body's immune response to an antigen) in influenza vaccines can improve immune responses, especially in high-risk groups like the elderly. This suggests that the A/H5 Influenza Vaccine, if adjuvanted, might be more effective in providing protection against influenza. ^{1 2 3 4 5}

Is the flu vaccine generally safe for humans?

Flu vaccines are generally safe, but they can cause rare serious side effects, like fever and febrile seizures in children, and have been linked to Guillain-Barré syndrome in the past. Most people experience only mild symptoms, and safety monitoring continues to ensure any new concerns are quickly identified. ^{6 7 8 9 10}

How is the A/H5 Influenza Vaccine different from other flu vaccines?

The A/H5 Influenza Vaccine is unique because it targets the H5 subtype of the influenza virus, which is a potential pandemic strain. Unlike traditional flu vaccines, it often requires adjuvants (substances that enhance the body's immune response) to be effective, and oil-in-water adjuvants have shown to significantly boost immune responses compared to nonadjuvanted versions. ^{3 11 12 13 14}

What is the purpose of this trial?

This BARDA-sponsored, randomized, double-blind, phase 2 study is designed to assess safety and immunogenicity of A/H5 inactivated monovalent influenza vaccines at different antigen dose levels adjuvanted with AS03 or MF59.

Eligibility Criteria

Adults over 18, in stable health, who can consent to the study and agree to have samples stored for future research. Women of childbearing age must use effective birth control. Those with chronic conditions can join if their health is expected to remain stable.

Inclusion Criteria

My chronic conditions are stable and well-managed.

I can attend all study visits and won't move away during the study.

Willing and able to provide written informed consent prior to initiation of study procedures

Exclusion Criteria

I have received a blood product or immunoglobulin within the last 3 months.

I have been using glucocorticoids regularly for the last month.

My lab tests or health conditions won't affect the study's safety or results.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two doses of adjuvanted vaccine separated by 21 days

6 weeks

2 visits (in-person)

Safety Assessment

Safety assessments based on solicited AEs, unsolicited TEAEs, and treatment-emergent SAEs, pIMDs, and MAAEs

29 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• A/H5 Influenza Vaccine

Trial Overview The trial tests various doses of H5N8 and H5N1 influenza vaccines combined with AS03 or MF59 adjuvants. It's a phase 2 study assessing safety and how well these vaccines work at different dose levels.

Participant Groups

Group I: Treatment Group O Experimental Treatment 1 Intervention

This treatment group of 60 participants (age ≥65) will receive 15 µg of Egg-A/bar-headed goose/Qinghai Lake/1A/2005 (H5N1) adjuvanted with MF59.

Group II: Treatment Group N Experimental Treatment 1 Intervention

This treatment group of 120 participants (60 participants ages 18-64 and 60 participants age ≥65) will receive 7.5 µg of Egg-A/bar-headed goose/Qinghai Lake/1A/2005 (H5N1) adjuvanted with MF59.

Group III: Treatment Group M Experimental Treatment 1 Intervention

This treatment group of 60 participants (ages 18-64) will receive 3.75 µg of Egg-A/bar-headed goose/Qinghai Lake/1A/2005 (H5N1) adjuvanted with MF59.

Group IV: Treatment Group L Experimental Treatment 1 Intervention

This treatment group of 60 participants (ages ≥65) will receive 15 µg of Egg-A/bar-headed goose/Qinghai Lake/1A/2005 adjuvanted with a full dose of AS03A.

Group V: Treatment Group K Experimental Treatment 1 Intervention

This treatment group of 120 participants (60 participants ages 18-64 and 60 participants age ≥65) will receive 7.5 µg of Egg-A/bar-headed goose/Qinghai Lake/1A/2005 (H5N1) adjuvanted with a full dose of AS03A.

Group VI: Treatment Group J Experimental Treatment 1 Intervention

This treatment group of 60 participants (ages 18-64) will receive 3.75 µg of Egg-A/bar-headed goose/Qinghai Lake/1A/2005 (H5N1) adjuvanted with a full dose of AS03A.

Group VII: Treatment Group I Experimental Treatment 1 Intervention

This treatment group of 120 participants (60 participants ages 18-64 and 60 participants age ≥65) will receive 15 µg of Egg-A/Astrakhan/3212/2020 (H5N8) adjuvanted with MF59.

Group VIII: Treatment Group H Experimental Treatment 1 Intervention

This treatment group of 120 participants (60 participants ages 18-64 and 60 participants age ≥65) will receive 7.5 µg of Egg-A/Astrakhan/3212/2020 (H5N8) adjuvanted with MF59.

Group IX: Treatment Group G Experimental Treatment 1 Intervention

This treatment group of 60 participants (ages 18-64) will receive 3.75 µg of Egg-A/Astrakhan/3212/2020 (H5N8) adjuvanted with MF59.

Group X: Treatment Group F Experimental Treatment 1 Intervention

This treatment group of 120 participants (60 participants ages 18-64 and 60 participants age ≥65 will receive 15 µg of Egg-A/Astrakhan/3212/2020 (H5N8) adjuvanted with a half dose of AS03A.

Group XI: Treatment Group E Experimental Treatment 1 Intervention

This treatment group of 120 participants (60 participants ages 18-64 and 60 participants age ≥65) will receive 7.5 µg of Egg-A/Astrakhan/3212/2020 (H5N8) adjuvanted with a half dose of AS03A.

Group XII: Treatment Group D Experimental Treatment 1 Intervention

This treatment group of 60 participants (ages 18-64) will receive 3.75 µg of Egg-A/Astrakhan/3212/2020 (H5N8) adjuvanted with a half dose of AS03A.

Group XIII: Treatment Group C Experimental Treatment 1 Intervention

This treatment group of 120 participants (60 participants ages 18-64 and 60 participants age ≥65) will receive 15 µg of Egg-A/Astrakhan/3212/2020 (H5N8) adjuvanted with a full dose of AS03A.

Group XIV: Treatment Group B Experimental Treatment 1 Intervention

This treatment group of 120 participants (60 participants ages 18-64 and 60 participants ages ≥65) in Treatment Group B will receive 7.5 µg of Egg-A/Astrakhan/3212/2020 (H5N8) adjuvanted with a full dose of AS03A.

Group XV: Treatment Group A Experimental Treatment 1 Intervention

This treatment group of 60 participants (ages 18-64) in Treatment Group A will receive 3.75 µg of Egg-A/Astrakhan/3212/2020 (H5N8) antigen adjuvanted with a full dose of AS03A.

Who Is Running the Clinical Trial?

Biomedical Advanced Research and Development Authority

Lead Sponsor

Trials

108

Recruited

574,000+

Rho Federal Systems Division, Inc.

Industry Sponsor

Trials

44

Recruited

15,000+

ICON plc

Industry Sponsor

Trials

88

Recruited

28,900+

Dr. Steve Cutler

ICON plc

Chief Executive Officer since 2017

PhD from the University of Sydney, MBA from the University of Birmingham

Dr. Greg Licholai

ICON plc

Chief Medical Officer since 2023

Degrees from Harvard Business School, Yale School of Medicine, Columbia University, and Boston College

Findings from Research

The A/H5N2 live attenuated influenza vaccine was found to be safe and well tolerated in a phase I clinical trial with 40 healthy volunteers, showing no increased rates of adverse events.

The vaccine demonstrated strong immunogenicity, with 96.6% of participants showing an immune response and significant seroconversion rates (37.9% and 48.3%) four weeks after the second dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical testing of pre-pandemic live attenuated A/H5N2 influenza candidate vaccine in adult volunteers: results from a placebo-controlled, randomized double-blind phase I study. Rudenko, L., Kiseleva, I., Stukova, M., et al.[2022]

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]

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]

References

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

Selection of an adjuvant for seasonal influenza vaccine in elderly people: modelling immunogenicity from a randomized trial. [2021]

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

Adjuvanted influenza vaccines. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical testing of pre-pandemic live attenuated A/H5N2 influenza candidate vaccine in adult volunteers: results from a placebo-controlled, randomized double-blind phase I study. [2022]

4. Canada pubmed.ncbi.nlm.nih.gov

Who and when to vaccinate against influenza. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Effects of influenza vaccination on the risk of cardiovascular and respiratory diseases and all-cause mortality. [2021]

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

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

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

The safety of influenza vaccines in children: An Institute for Vaccine Safety white paper. [2016]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Participant centred safety surveillance of health care workers receiving influenza vaccination. [2020]

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

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

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

Serious adverse events following receipt of trivalent inactivated influenza vaccine in Korea, 2003-2010. [2013]

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

Immunogenicity, Safety, and Efficacy of a Standalone Universal Influenza Vaccine, FLU-v, in Healthy Adults: A Randomized Clinical Trial. [2020]

12. Germany pubmed.ncbi.nlm.nih.gov

Vaccines for pandemic influenza: summary of recent clinical trials. [2016]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Stable emulsion (SE) alone is an effective adjuvant for a recombinant, baculovirus-expressed H5 influenza vaccine in healthy adults: A Phase 2 trial. [2017]

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

Strategies for developing vaccines against H5N1 influenza A viruses. [2019]