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

(Engage Trial)

No longer recruiting at 53 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new E. coli vaccine, ExPEC9V, and a high-dose flu vaccine can work together without losing effectiveness. Researchers aim to ensure that combining these vaccines doesn't weaken the body's response to either. The trial seeks individuals in stable health who do not anticipate major medical changes or hospital stays soon. Participants must also be postmenopausal and not planning to conceive. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking vaccine advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the ExPEC9V vaccine has not raised any safety concerns in studies. No unexpected side effects or reactions were reported in participants from earlier research.

Similarly, the high-dose quadrivalent influenza vaccine (HD QIV) is recognized for its safety. It has undergone thorough testing in older adults and is generally well-tolerated. Common side effects are usually mild, such as pain or redness at the injection site.

Both vaccines have been used safely, and current research supports their safety in humans. This suggests they are generally safe for use in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ExPEC9V because, unlike standard vaccines that primarily protect against respiratory influenza, it targets extraintestinal pathogenic Escherichia coli (ExPEC), a common cause of blood infections. The novel aspect of ExPEC9V is its ability to prevent infections caused by ExPEC, which current flu vaccines do not address. By combining ExPEC9V with a high-dose influenza vaccine, this approach offers dual protection against both E. coli and flu, potentially reducing the burden of these infections more effectively than existing options.

What evidence suggests that this trial's treatments could be effective for E. coli and influenza prevention?

Research has shown that the high-dose quadrivalent influenza vaccine (HD QIV), which participants in this trial may receive, offers 24.2% better protection against the flu in older adults compared to the standard dose. It also lowers the risk of hospitalization for respiratory or heart issues. The ExPEC9V vaccine, another treatment option in this trial, is under development to prevent serious E. coli infections; however, recent reports indicate limited effectiveness so far. This study examines whether these vaccines can be used together without compromising each other's effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Janssen Research & Development LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04899336

NCT04899336 | A Study of Vaccination With 9-valent ... The purpose of this study is to demonstrate the efficacy of 9-valent extraintestinal pathogenic Escherichia coli vaccine (ExPEC9V) compared to placebo.

2. sanofi.com sanofi.com/en/media-room/press-releases/2025/2025-02-13-06-00-00-3025576

Update on extraintestinal pathogenic E. coli vaccine phase ... Sanofi and Johnson & Johnson's vaccine candidate for extraintestinal pathogenic E. coli was not sufficiently effective at preventing invasive E. coli disease ( ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11152113/

Vaccines against extraintestinal pathogenic Escherichia ... To this end, we evaluated 27 prospective human vaccine trials for ExPEC-associated disease with endpoints for safety, immunogenicity, and/or protective efficacy ...

4. horizonscandb.pcori.org horizonscandb.pcori.org/report/topics/927

ExPEC9V to prevent invasive Escherichia coli disease ExPEC9V is a vaccine under development to prevent invasive Escherichia coli disease caused by extraintestinal pathogenic E coli (ExPEC).

5. jnj.com jnj.com/media-center/press-releases/johnson-johnson-statement-on-phase-3-e-mbrace-study

Johnson & Johnson Statement on Phase 3 E.mbrace Study Independent, scheduled review finds investigational vaccine regimen lacks efficacy in preventing invasive E. coli disease (IED). No safety signals identified.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0924857925001621

Extraintestinal pathogenic Escherichia coli (ExPEC) O ... In this study, 82.2% and 10.7% of ExPEC isolates were tested as multidrug-resistant (MDR) and carbapenem-resistant E. coli, respectively. •. The ...