ExPEC9V + High-Dose Flu Vaccine for E. coli and Influenza Prevention

(Engage Trial)

Recruiting at 48 trial locations

Age: 65+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Uncontrolled chronic conditions, Severe allergies, Major surgery, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 2

959 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must be medically stable, meaning your condition should not require significant changes in therapy for 6 weeks before joining the trial.

What data supports the effectiveness of the treatment ExPEC9V + High-Dose Flu Vaccine for E. coli and Influenza Prevention?

Research shows that high-dose influenza vaccines provide better protection against the flu in older adults compared to standard doses, even when the vaccine strains don't perfectly match the circulating virus. This suggests that the high-dose flu vaccine component of the treatment could be effective in preventing influenza. ^{1 2 3 4 5}

What safety data exists for the ExPEC9V + High-Dose Flu Vaccine treatment?

The high-dose quadrivalent influenza vaccines, including those with different formulations, have shown good safety profiles in various studies. Most adverse reactions were mild to moderate and resolved quickly, with no serious adverse events linked to the vaccines. ^{6 7 8 9 10}

How is the ExPEC9V + High-Dose Flu Vaccine treatment different from other treatments for E. coli and influenza prevention?

The ExPEC9V + High-Dose Flu Vaccine is unique because it combines a vaccine targeting specific E. coli strains with a high-dose influenza vaccine, aiming to prevent both E. coli infections and influenza, whereas traditional treatments typically target only one of these infections separately. ^{4 6 7 11 12}

What is the purpose of this trial?

This trial is testing if a high-dose flu shot and an E. coli vaccine can be given together without reducing their effectiveness. It targets people who need both vaccines, ensuring that the immune system can still recognize and fight off both flu viruses and E. coli bacteria.

Research Team

Janssen Research & Development LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults aged 65 or older who are medically stable, understand the study's risks and benefits, agree not to donate blood during the study period, and women must be postmenopausal. Participants should not expect hospitalization soon and must follow lifestyle restrictions.

Inclusion Criteria

You should be in good health and not expected to need hospitalization during the study. Your medical condition should have been stable for at least 6 weeks before joining the study.

I am willing to sign a consent form understanding the study's risks and benefits.

I agree not to donate blood until 3 months after my last vaccine dose.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination Phase 1

Participants receive the first vaccination, either coadministration of ExPEC9V and HD QIV or HD QIV with placebo

1 day

1 visit (in-person)

Observation and Monitoring

Participants are monitored for solicited systemic and local adverse events for 14 days post-vaccination

14 days

Vaccination Phase 2

Participants receive the second vaccination, either ExPEC9V or placebo, depending on the group

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including antibody titers, for 29 days after each vaccination

29 days

Long-term Follow-up

Participants are monitored for serious adverse events and medically-attended adverse events until 6 months after the second vaccination

6 months

Treatment Details

Interventions

• ExPEC9V
• HD quadrivalent influenza vaccine

Trial Overview The study tests if a high-dose flu vaccine (HD QIV) affects antibody response when given with a new E. coli vaccine (ExPEC9V), compared to each vaccine given alone in seniors.

Participant Groups

Group I: Group 2: Control Group Experimental Treatment 3 Interventions

Participants will receive IM injection of matching placebo along with HD quadrivalent influenza vaccine, concomitantly, on Day 1 and ExPEC9V on Day 30.

Group II: Group 1: Coadministration (CoAd) Group Experimental Treatment 3 Interventions

Participants will receive intramuscular (IM) injection of 9-valent extraintestinal pathogenic Escherichia coli vaccine (ExPEC9V) along with high-dose (HD) quadrivalent influenza vaccine, concomitantly, on Day 1 and placebo on Day 30.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

High-dose trivalent inactivated influenza vaccine (HD-IIV3) and recombinant trivalent influenza vaccine (RIV) may improve vaccine effectiveness in adults aged 50-64 who are at high risk for influenza complications, suggesting a potential public health benefit.

The analysis indicates that using HD-IIV3 or RIV for high-risk patients could be a cost-effective strategy, with the HD-IIV3 & SD-IIV4 strategy costing $71,500 per quality-adjusted life year (QALY) gained, highlighting the economic viability of these vaccines in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness and public health impact of alternative influenza vaccination strategies in high-risk adults. Raviotta, JM., Smith, KJ., DePasse, J., et al.[2018]

The high-dose inactivated influenza vaccine quadrivalent (HD-IIV4) has been shown to be safe and effective in preventing influenza in adults aged 65 and older, with improved immunogenicity against additional B strains compared to standard vaccines.

Despite some increased adverse reactions like injection-site pain and myalgia, HD-IIV4 is recommended as the vaccine of choice for older adults due to its superior efficacy compared to other influenza vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Inactivated Influenza Vaccine Quadrivalent for Older Adults. Chahine, EB.[2021]

OVX836, a recombinant influenza vaccine, demonstrated a favorable safety profile up to a dose of 480 μg, with mild local and systemic reactions, indicating it is well tolerated by healthy adults.

The vaccine elicited significant dose-dependent immune responses, including increased nucleoprotein-specific CD4 and CD8 T-cell responses, suggesting it may provide effective protection against influenza A and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity, safety, and preliminary efficacy evaluation of OVX836, a nucleoprotein-based universal influenza A vaccine candidate: a randomised, double-blind, placebo-controlled, phase 2a trial. Leroux-Roels, I., Willems, P., Waerlop, G., et al.[2023]

In a safety surveillance study of the 2021/22 MF59-adjuvanted quadrivalent influenza vaccine (aQIV) among 1,059 older adults in Italy, only one non-serious adverse event (a case of pyrexia) was reported, resulting in a very low rate of 0.9 per 1,000 doses administered.

The study confirmed that the reactogenicity profile of aQIV is consistent with the established safety profile of the previous trivalent formulation, which may enhance public confidence in influenza vaccination and improve vaccination rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced passive safety surveillance of the MF59-adjuvanted quadrivalent influenza vaccine in the elderly during the 2021/22 influenza season. Amicizia, D., Domnich, A., Lai, PL., et al.[2023]

In a study involving 741 healthcare workers, the cell-based quadrivalent vaccine Flucelvax Tetra was found to have a high safety profile, with 99.8% of reported adverse events classified as not serious.

Out of 430 adverse events following immunization, only one was serious, and causality assessment indicated it was not linked to the vaccine, suggesting that Flucelvax Tetra is safe for use in healthcare settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Marketing Active Surveillance of Adverse Reactions Following Influenza Cell-Based Quadrivalent Vaccine: An Italian Prospective Observational Study. Stefanizzi, P., De Nitto, S., Spinelli, G., et al.[2021]

The high-dose quadrivalent inactivated influenza vaccine (HD-QIV) demonstrated excellent immunogenicity in healthy adults aged 19-64, achieving 100% seroprotection for A/H1N1 and high seroconversion rates for other strains, indicating strong immune response.

The HD-QIV was found to be safe and well-tolerated, with no serious adverse events reported, making it a promising option for enhancing influenza protection in the adult population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, single-blind, active-controlled phase I clinical trial to evaluate the immunogenicity and safety of GC3114 (high-dose, quadrivalent influenza vaccine) in healthy adults. Noh, JY., Jang, YS., Lee, SN., et al.[2020]

In a study involving 2670 healthy adults aged 65 and older, the quadrivalent high-dose influenza vaccine (IIV4-HD) demonstrated non-inferior immunogenicity compared to the licensed trivalent high-dose vaccine (IIV3-HD) for all four influenza strains.

IIV4-HD showed superior immune responses for both B strains compared to IIV3-HD that did not contain the same B-lineage strain, while maintaining a similar safety profile, indicating it is a more effective option without added safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults ≥65 years of age: A phase 3 randomized clinical trial. Chang, LJ., Meng, Y., Janosczyk, H., et al.[2020]

References

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

Cost-effectiveness and public health impact of alternative influenza vaccination strategies in high-risk adults. [2018]

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

High-Dose Influenza Vaccine Is Associated With Reduced Mortality Among Older Adults With Breakthrough Influenza Even When There Is Poor Vaccine-Strain Match. [2023]

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

A Randomized, Double-blind, Active-controlled Phase III Trial of a Cell Culture-derived Quadrivalent Inactivated Influenza Vaccine in Healthy South Korean Children and Adolescents 6 Months to 18 Years of Age. [2020]

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

High-Dose Inactivated Influenza Vaccine Quadrivalent for Older Adults. [2021]

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

Modelling the population-level benefits and cost-effectiveness of cell-based quadrivalent influenza vaccine for children and adolescents aged 6 months to 17 years in the US. [2023]

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

Immunogenicity and safety of an egg culture-based quadrivalent inactivated non-adjuvanted subunit influenza vaccine in subjects ≥3 years: A randomized, multicenter, double-blind, active-controlled phase III, non-inferiority trial. [2022]

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

Immunogenicity, safety, and preliminary efficacy evaluation of OVX836, a nucleoprotein-based universal influenza A vaccine candidate: a randomised, double-blind, placebo-controlled, phase 2a trial. [2023]

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

Enhanced passive safety surveillance of the MF59-adjuvanted quadrivalent influenza vaccine in the elderly during the 2021/22 influenza season. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Post-Marketing Active Surveillance of Adverse Reactions Following Influenza Cell-Based Quadrivalent Vaccine: An Italian Prospective Observational Study. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Adjuvanted recombinant hemagglutinin H7 vaccine to highly pathogenic influenza A(H7N9) elicits high and sustained antibody responses in healthy adults. [2021]

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

Randomized, single-blind, active-controlled phase I clinical trial to evaluate the immunogenicity and safety of GC3114 (high-dose, quadrivalent influenza vaccine) in healthy adults. [2020]

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

Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults ≥65 years of age: A phase 3 randomized clinical trial. [2020]