ExPEC9V Vaccine for E. coli Infections Prevention

Recruiting in Palo Alto (17 mi)

+285 other 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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Burke Primary Care Morganton, NC

Colchester Research Hospital Truro, Canada

PMG Research of Bristol Bristol, TN

Wellington Medical Center Hamilton, Canada

More Trial Locations

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1022

Patients Recruited

6,408,000+

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] Label="Background" NlmCategory="UNASSIGNED">ExPEC10V is a bioconjugate vaccine containing O-antigen polysaccharides of 10 extraintestinal pathogenic Escherichia coli (ExPEC) serotypes. This phase 1/2a study (NCT03819049) assessed the safety, reactogenicity, and immunogenicity of ExPEC10V (VAC52416) to prevent invasive E coli disease in elderly adults.

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] Escherichia coli infections are increasing worldwide in community and hospital settings. The E coli O-antigen is a promising vaccine target. We aimed to assess the safety and immunogenicity of a bioconjugate vaccine containing the O-antigens of four E coli serotypes (ExPEC4V).

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] Extraintestinal pathogenic Escherichia coli (ExPEC) is the most common gram-negative bacterial pathogen in humans. ExPEC causes the vast majority of urinary tract infections (UTIs), is a leading cause of adult bacteremia, and is the second most common cause of neonatal meningitis. Increasing multidrug resistance among ExPEC strains constitutes a major obstacle to treatment and is implicated in increasing numbers of hospitalizations and deaths and increasing healthcare costs associated with ExPEC infections. An effective vaccine against ExPEC infection is urgently needed. The O antigen, a component of the surface lipopolysaccharide, has been identified as a promising vaccine target. With the availability of a novel bioconjugation technology it is expected that multivalent O antigen conjugate vaccines can be produced at industrial scale. Clinical proof of concept of a 4-valent O antigen conjugate vaccine is ongoing. An ExPEC vaccine effective against strains that are associated with major diseases and resistant to multiple drugs could be routinely delivered to individuals at risk of developing severe E. coli infection, such as elderly people, individuals undergoing abdominal surgery and prostatic biopsy procedures, and persons at risk of recurrent and/or complicated UTI.

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] Invasive extraintestinal pathogenic Escherichia coli (ExPEC) disease (IED), characterised by sepsis and bacteraemia, is a major global healthcare concern worsened by emerging multidrug resistant (MDR) strains. The development of multivalent prophylactic vaccines targeting E. coli strains of IED-associated O-serotypes could address this. A better understanding of O-serotype distribution is required for this purpose. Here, we characterised O-serotype prevalence and drug resistance among ExPEC bacteraemia isolates in Japan.

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] ExPEC4V (JNJ-63871860) is a bioconjugate vaccine, containing O-antigens from Escherichia coli serotypes O1A, O2, O6A, and O25B, developed for the prevention of invasive extra-intestinal pathogenic E coli (ExPEC) disease. We aimed to assess safety, reactogenicity, and immunogenicity of ExPEC4V in healthy adults.

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] Infections due to extraintestinal pathogenic E. coli (ExPEC) result in significant morbidity, mortality and increased healthcare costs. An efficacious vaccine against ExPEC would be desirable. In this report, we explore the use of killed-whole E. coli as a vaccine immunogen. Given the diversity of capsule and O-antigens in ExPEC, we have hypothesized that alternative targets are viable vaccine candidates. We have also hypothesized that immunization with a genetically engineered strain that is deficient in the capsule and O-antigen will generate a greater immune response against antigens other than the capsular and O-antigen epitopes than a wild-type strain. Lastly, we hypothesize that mucosal immunization with killed E. coli has the potential to generate a significant immune response. In this study, we demonstrated that nasal immunization with a formalin-killed ExPEC derivative deficient in capsule and O-antigen results in a significantly greater overall humoral response compared to its wild-type derivative (which demonstrates that capsule and/or the O-antigen impede the development of an optimal humoral immune response) and a significantly greater immune response against non-capsular and O-antigen epitopes. These antibodies also bound to a subset of heterologous ExPEC strains and enhanced neutrophil-mediated bactericidal activity against the homologous and a heterologous strain. Taken together, these studies support the concept that formalin-killed genetically engineered ExPEC derivatives are whole cell vaccine candidates to prevent infections due to ExPEC.