A Study of Vaccination With 9-valent Extraintestinal Pathogenic Escherichia Coli Vaccine (ExPEC9V) in the Prevention of Invasive Extraintestinal Pathogenic Escherichia Coli Disease in Adults Aged 60 Years And Older With a History of Urinary Tract Infection in the Past 2 Years

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the efficacy of 9-valent extraintestinal pathogenic Escherichia coli vaccine (ExPEC9V) compared to placebo in the prevention of the first invasive extraintestinal pathogenic Escherichia coli disease (IED) event caused by ExPEC9V O-serotypes.

Detailed Description
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Invasive extraintestinal pathogenic Escherichia coli disease (IED) is defined as an acute illness consistent with systemic bacterial infection, which is microbiologically confirmed either by the isolation and identification of Escherichia coli (E. coli) from blood or any other sterile body sites, or by the isolation and identification of E. coli from urine in a participant with urosepsis and no other identifiable source of infection. ExPEC9V (JNJ-78901563, primary compound number: VAC52416) is a 9-valent vaccine candidate in development for active immunization for the prevention of IED in adults 60 years of age and older. Although IED affects all ages, adults aged greater than or equal to (>=) 60 years have an increased risk of developing IED, including bacteremia and sepsis, which can be community-acquired, hospital-acquired or healthcare associated. As the mechanism of action of conjugate vaccines in the prevention of invasive disease is not expected to be affected by antibiotic resistance mechanisms, that is, resistance mechanisms are not linked to O-polysaccharide structures, the sponsor has no reason to expect a difference in outcome of efficacy between antimicrobial-resistant and susceptible O-serotypes. This study incorporates an inferentially seamless group-sequential design. This study consists of a Screening Phase (selected screening procedures may be performed up to 8 days prior to vaccination on Day 1), Randomization, Vaccination Phase (Day 1) and Follow-up Phase (up to 3 years post-vaccination). The total study duration is approximately up to 6 years 11 months. Key safety assessments include serious adverse events (SAEs), solicited and unsolicited adverse events (AEs), physical examination, and vital signs.

Official Title
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Randomized, Double-blind, Placebo-controlled, Multicenter Phase 3 Study to Assess the Efficacy, Safety And Immunogenicity of Vaccination With ExPEC9V in the Prevention of Invasive Extraintestinal Pathogenic Escherichia Coli Disease in Adults Aged 60 Years And Older With a History of Urinary Tract Infection in the Past 2 Years

Conditions
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Invasive Extraintestinal Pathogenic Escherichia Coli Disease (IED) Prevention

Intervention / Treatment
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* Biological: ExPEC9V
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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 Participant must have a history of UTI in the past 2 years for which evidence of diagnosis was verified by the investigator. In case of a recent history of UTI or ABP, the condition must have resolved greater than (>)14 days prior to randomization Before randomization, participants who were born female must be either postmenopausal or permanently sterile, and not intending to conceive by any methods Participant must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study Exclusion Criteria: Participant has end-stage renal disease for which dialysis is required Participant has a contraindication to intramuscular (IM) injections and blood draws example, due to bleeding disorders or a history of difficult blood draws Participant has a history of acute polyneuropathy (for example, Guillain-Barre syndrome) or chronic inflammatory demyelinating polyneuropathy Participant has received any Escherichia coli (E. coli) or extraintestinal pathogenic Escherichia coli (ExPEC) vaccine

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ExPEC9V<br>Participants will receive a single intramuscular (IM) injection of 9-valent extraintestinal pathogenic Escherichia coli vaccine (ExPEC9V) on Day 1. | Biological: ExPEC9V<br>* ExPEC9V will be administered as an IM injection.<br>* Other names: VAC52416, JNJ-78901563;|
| Placebo Comparator: Placebo<br>Participants will receive a single IM injection of matching placebo on Day 1. | Other: Placebo<br>* Matching placebo will be administered as an IM injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with First Invasive Extraintestinal Pathogenic E.coli Disease(IED) Event with Microbiological Confirmation in Blood, Other Sterile Sites, or Urine, Caused by 9-valent Extraintestinal Pathogenic E. coli Vaccine (ExPEC9V) O-serotypes | Number of participants with first IED event, with microbiological confirmation in blood, other sterile sites, or urine, caused by ExPEC9V O-serotypes will be reported. | Up to 3 years | 
| Number of Participants with First IED Event with Microbiological Confirmation in Blood or Other Sterile Sites Caused by ExPEC9V O-serotypes | Number of participants with first IED event with microbiological confirmation in blood or other sterile sites, excluding IED cases with microbiological confirmation from urine only, caused by ExPEC9V O-serotypes will be reported. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with All IEDs (Including Multiple IEDs per Participant) Caused by ExPEC9V O-serotypes | Number of participants with all IEDs (including multiple IEDs per participant) caused by ExPEC9V O-serotypes will be reported. | Up to 3 years | 
| Number of Participants with First Hospitalized IED Event Caused by ExPEC9V O-serotypes | Number of participants with first hospitalized IED event caused by ExPEC9V O-serotypes will be reported. | Up to 3 years | 
| Number of Participants with First IED Event Meeting Criteria for Sepsis Caused by ExPEC9V O-serotypes | Number of participants with first IED event meeting criteria for sepsis caused by ExPEC9V O-serotypes will be reported. | Up to 3 years | 
| Number of Participants with First Bacteremic IED Event Caused by ExPEC9V O-serotypes | Number of participants with first bacteremic IED event caused by ExPEC9V O-serotypes will be reported. | Up to 3 years | 
| Number of Participants with First Pyelonephritis Event Caused by ExPEC9V O-serotypes | Number of participants with first pyelonephritis event caused by ExPEC9V O-serotypes will be reported. | Up to 3 years | 
| Number of Participants with First Urinary Tract Infection (UTI) Event Caused by ExPEC9V O-serotypes | Number of participants with first UTI event caused by ExPEC9V O-serotypes will be reported. | Up to 3 years | 
| Number of Participants with All UTIs (Including Multiple UTIs per Participant) Caused by ExPEC9V O-serotypes | Number of participants with all UTIs (including multiple UTIs per participant) caused by ExPEC9V O-serotypes will be reported. | Up to 3 years | 
| Number of Participants with First IED Event Caused by Escherichia coli (E.coli) | Number of participants with first IED event caused by E.coli will be reported. | Up to 3 years | 
| Number of Participants with First Pyelonephritis Event caused By E.coli | Number of participants with first pyelonephritis event caused by E.coli will be reported. | Up to 3 years | 
| Number of Participants with First UTI Event caused by E.coli | Number of participants with first UTI event caused by E.coli will be reported. | Up to 3 years | 
| Antibody Titers to Vaccine O-serotype Antigens as Determined by Multiplex Electrochemiluminescent (ECL)-based Immunoassay | Antibody titers to vaccine O-serotype antigens as determined by multiplex ECL-based immunoassay will be reported. | Up to 3 years | 
| Antibody Titers to Genetically Detoxified Form of Exotoxin A Derived from Pseudomonas Aeruginosa (EPA) as Determined by Multiplex ECL-based Immunoassay | Antibody titers to EPA as determined by multiplex ECL-based immunoassay will be reported. | Up to 3 years | 
| Antibody Titers to Vaccine O-serotype Antigens as Determined by Multiplex Opsonophagocytic Assay (MOPA) | Antibody titers to vaccine O-serotype antigens as determined by MOPA will be reported. | Up to 3 years | 
| Number of Participants with Solicited Local Adverse Events (AEs) | Number of participants with solicited local AEs will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs are pre-defined local (at the injection site) AEs. Participants will be asked to note in the diary occurrences of injection site pain/tenderness, erythema and swelling at the study vaccine injection site daily for 14 days post-vaccination (day of vaccination and the subsequent 14 days). | Up to Day 15 (until 14 days post-vaccination) | 
| Number of Participants with Solicited Systemic AEs | Number of participants with solicited systemic AEs will be reported. Participants will be instructed on how to record daily temperature using a thermometer and also instructed to note signs and symptoms in the diary on a daily basis for 14 days post-vaccination (day of vaccination and the subsequent 14 days). Solicited systemic AEs are fatigue, headache, nausea, and myalgia. | Up to Day 15 (until 14 days post-vaccination) | 
| Number of Participants with Unsolicited AEs | Number of participants with unsolicited AEs will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary. | Up to Day 30 (until 29 days post-vaccination) | 
| Number of Participants with Serious Adverse Events (SAEs) | A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important. | Up to 3 years | 
| Short Form-36 (SF-36) Total Scores | The SF-36 is a 36-item questionnaire with a recall period for all items of 1 week. The SF 36 version 2 includes 8 domains that measure physical functioning, role limitations due to physical health problems, bodily pain, general health (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE) and mental health (MH). The 8 domains can be aggregated into 2 summary scales that reflect physical and mental health: a physical component summary (PCS) and a mental component summary (MCS). Responses to all items are rated on a 3-, 5- or 6-point Likert scale. The scores range from 0 (lowest or worst possible level of functioning) to 100 (highest or best possible level of functioning). | Up to 3 years | 
| European Quality of Life (EuroQol) 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Scores | The EQ-5D-5L is a standardized measure of health status. It is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating health today with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). | Up to 3 years | 
| Change from Baseline in Frailty Index | Frailty will be assessed at baseline based on Short Physical Performance Battery (SPPB) score and will be calculated using participants self-reported information regarding health status (components of SF-36 and EQ-5D), and baseline health conditions collected through medical conditions of interest. The specific medical conditions of interest used for the calculation of the frailty index score will include: diabetes mellitus, history of myocardial infarction, congestive heart failure, hypertension, history of cerebrovascular disease (sequelae of stroke), chronic obstructive pulmonary disease (COPD), cancer, osteoarthritis or rheumatoid arthritis, gastric or duodenal ulcer, long term disability or handicap, hearing problems, migraine, cataract, and glaucoma. Total Frailty Index, ranging from 0 (not frail or best possible score) to 43 (frail or worst possible score), will be calculated as accumulation of individual's deficits. | Baseline to 3 years | 
| Medical Resource Utilization (MRU) for IED Events | MRU for IED events will be reported. | Up to Day 366 Post-IED | 
| MRU for UTI Events | MRU for UTI events (for immunogenicity subset only that is for participants from selected study sites who have given informed consent prior to randomization for additional immunogenicity assessments) will be reported. | Up to Day 29 Post-UTI | 
| MRU for Acute Bacterial Prostatitis (ABP) | Medical resource utilization for ABP events (for immunogenicity subset only that is for participants from selected study sites who have given informed consent prior to randomization for additional immunogenicity assessments) will be reported. | Up to Day 29 Post-ABP | 
| Number of Participants with the Hospitalization for IED or, UTI, or ABP Events | Number of participants with hospitalization for IED or, UTI, or ABP events will be reported. | Up to 3 years | 
| Length of Stay in Hospital for IED, UTI, or ABP Events | Length of stay in hospital for IED, UTI, or ABP events will be reported. | Up to 3 years | 
| Number of Participants with the Intensive Care Unit (ICU) Hospitalization for IED or UTI or ABP Events | Number of participants with ICU hospitalization for IED or UTI or ABP events will be reported. | Up to 3 months | 
| Length of ICU Stay in Hospital for IED, UTI, or ABP Events | Length of ICU stay in hospital for IED, UTI, or ABP events will be reported. | Up to 3 months | 
| Number of Participants with IED-related and All-cause Mortality | Number of participants with IED-related and all-cause mortality will be reported. | Up to 3 years |