ExPEC9V Vaccine for E. coli Infections Prevention

Recruiting at285 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Janssen Research & Development, LLC

Disqualifiers: End-stage renal disease, Bleeding disorders, Polyneuropathy, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a vaccine to protect older adults from serious E. coli infections. The vaccine trains the immune system to recognize and fight off nine types of harmful E. coli bacteria. In earlier studies, a similar vaccine caused fever and/or diarrhea in some participants and provided limited protection against illness.

Do I need to stop my current medications for the ExPEC9V vaccine trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the ExPEC9V treatment for preventing E. coli infections?

Research on similar vaccines, like ExPEC10V and ExPEC4V, shows they are safe and can trigger an immune response (immunogenicity) against E. coli, which suggests that ExPEC9V might also be effective in preventing infections caused by this bacteria. ^{1 2 3 4 5}

How is the ExPEC9V vaccine different from other treatments for E. coli infections?

The ExPEC9V vaccine is unique because it targets multiple O-antigen serotypes of extraintestinal pathogenic E. coli, aiming to prevent infections by stimulating the immune system to recognize and fight these specific strains, unlike traditional treatments that often rely on antibiotics. ^{1 2 4 5 6}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

Adults aged 60+ with a history of UTI in the past 2 years can join this trial. They must be postmenopausal or sterile if born female, not planning to conceive, and able to use digital devices for communication. Excluded are those with bleeding disorders, certain neuropathies, previous E. coli vaccines, or needing dialysis.

Inclusion Criteria

Participant must be willing to share relevant medical information pertaining to medical history and to share medical records relevant to the medical events identified as suspected cases of invasive extraintestinal pathogenic Escherichia coli disease (IED), urinary tract infections (UTI), or acute bacterial prostatitis (ABP) occurring during the study observation period

I can provide ID and stay in touch with the study team.

I had a urinary tract infection (UTI) in the last 2 years, but it was resolved more than 14 days ago.

Exclusion Criteria

I require dialysis for my end-stage kidney disease.

Participant has a contraindication to intramuscular (IM) injections and blood draws example, due to bleeding disorders or a history of difficult blood draws

I have had Guillain-Barre syndrome or a similar nerve condition.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 8 days

1 visit (in-person)

Vaccination

Participants receive a single intramuscular injection of either the ExPEC9V vaccine or placebo

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after vaccination

Up to 4 years

Long-term Follow-up

Participants continue to be monitored for long-term safety and efficacy outcomes

Up to 6 years 9 months

Treatment Details

Interventions

• ExPEC9V (Cancer Vaccine)
• Placebo (Other)

Trial Overview The study tests whether a vaccine called ExPEC9V prevents invasive diseases caused by certain E. coli types better than a placebo in older adults who've had UTIs before.

Participant Groups

Group I: ExPEC9V Experimental Treatment 1 Intervention

Participants will receive a single intramuscular (IM) injection of 9-valent extraintestinal pathogenic Escherichia coli vaccine (ExPEC9V) on Day 1.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive a single IM injection of matching placebo on Day 1.

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

The ExPEC10V vaccine was found to be well tolerated in elderly adults, with adverse event rates comparable to those of the pneumococcal vaccine, indicating a favorable safety profile.

Immunogenicity results showed a strong antibody response to ExPEC10V over one year, although there was a limited response to serotype O8, suggesting that the high-dose ExPEC10V is the optimal formulation for preventing invasive E. coli disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Reactogenicity, Immunogenicity, and Dose Selection of 10-Valent Extraintestinal Pathogenic Escherichia coli Bioconjugate Vaccine (VAC52416) in Adults Aged 60-85 Years in a Randomized, Multicenter, Interventional, First-in-Human, Phase 1/2a Study. Fierro, CA., Sarnecki, M., Doua, J., et al.[2023]

The ExPEC4V vaccine, targeting four E. coli serotypes, was well tolerated in a phase 1b trial with 93 women, showing no serious adverse events and only mild to moderate side effects.

The vaccine induced strong immune responses, significantly increasing antibody levels against all targeted serotypes, and resulted in fewer urinary tract infections caused by any E. coli serotype compared to the placebo group, suggesting potential efficacy in preventing UTIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity, and preliminary clinical efficacy of a vaccine against extraintestinal pathogenic Escherichia coli in women with a history of recurrent urinary tract infection: a randomised, single-blind, placebo-controlled phase 1b trial. Huttner, A., Hatz, C., van den Dobbelsteen, G., et al.[2022]

Extraintestinal pathogenic Escherichia coli (ExPEC) is a major cause of urinary tract infections and other serious conditions, with rising multidrug resistance making treatment increasingly difficult.

A promising 4-valent O antigen conjugate vaccine is currently in clinical testing, which could provide effective protection against drug-resistant ExPEC strains, particularly for high-risk groups like the elderly and patients undergoing certain medical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extraintestinal Pathogenic Escherichia coli, a Common Human Pathogen: Challenges for Vaccine Development and Progress in the Field. Poolman, JT., Wacker, M.[2018]

In a study of 401 E. coli blood isolates from patients aged 60 and older in Japan, the O25 serotype was found to be the most prevalent (28.7%) and exhibited the highest levels of multidrug resistance, particularly to fluoroquinolones (84.3%).

The findings highlight the need for multivalent vaccines targeting prevalent and drug-resistant E. coli serotypes, especially O25B, to combat invasive extraintestinal pathogenic E. coli disease in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distribution of extraintestinal pathogenic Escherichia coli O-serotypes and antibiotic resistance in blood isolates collected from patients in a surveillance study in Japan. Matsumoto, T., Mikamo, H., Ohge, H., et al.[2022]

The ExPEC4V vaccine was well tolerated in a study of 848 healthy adults, with mild-to-moderate adverse events reported in 43% of vaccinated participants, compared to 35% in the placebo group, indicating a favorable safety profile.

The vaccine elicited strong immune responses, with over 80% of participants showing a significant increase in specific antibodies 15 days post-vaccination, and 66-71% maintaining this response after one year, demonstrating its potential efficacy in preventing invasive E. coli disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a vaccine for extra-intestinal pathogenic Escherichia coli (ESTELLA): a phase 2 randomised controlled trial. Frenck, RW., Ervin, J., Chu, L., et al.[2020]

Nasal immunization with a genetically engineered, formalin-killed strain of extraintestinal pathogenic E. coli (ExPEC) that lacks capsule and O-antigen produced a significantly stronger immune response compared to the wild-type strain, suggesting that these components hinder optimal immune activation.

The antibodies generated from this immunization not only targeted the engineered strain but also showed effectiveness against other ExPEC strains, enhancing neutrophil activity and supporting the potential of these killed whole-cell vaccines in preventing ExPEC infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A killed, genetically engineered derivative of a wild-type extraintestinal pathogenic E. coli strain is a vaccine candidate. Russo, TA., Beanan, JM., Olson, R., et al.[2018]

References

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

Safety, Reactogenicity, Immunogenicity, and Dose Selection of 10-Valent Extraintestinal Pathogenic Escherichia coli Bioconjugate Vaccine (VAC52416) in Adults Aged 60-85 Years in a Randomized, Multicenter, Interventional, First-in-Human, Phase 1/2a Study. [2023]

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

Safety, immunogenicity, and preliminary clinical efficacy of a vaccine against extraintestinal pathogenic Escherichia coli in women with a history of recurrent urinary tract infection: a randomised, single-blind, placebo-controlled phase 1b trial. [2022]

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

Extraintestinal Pathogenic Escherichia coli, a Common Human Pathogen: Challenges for Vaccine Development and Progress in the Field. [2018]

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

Distribution of extraintestinal pathogenic Escherichia coli O-serotypes and antibiotic resistance in blood isolates collected from patients in a surveillance study in Japan. [2022]

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

Safety and immunogenicity of a vaccine for extra-intestinal pathogenic Escherichia coli (ESTELLA): a phase 2 randomised controlled trial. [2020]

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

A killed, genetically engineered derivative of a wild-type extraintestinal pathogenic E. coli strain is a vaccine candidate. [2018]