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
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 18,556
- 试验地点
- 13
- 主要终点
- 1-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
研究概览
简要总结
Invasive extraintestinal pathogenic Escherichia coli (ExPEC) disease 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), Vaccination Phase (Day 1) and Follow-up Phase (up to 3 years post-vaccination). The total study duration is up to 6 years and 4 months. Key safety assessments include serious adverse events (SAEs), solicited and unsolicited adverse events (AEs), physical examination, and vital signs
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 60.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1- 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.
- •2- 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, the condition must have resolved greater than (>)14 days prior to randomization.
- •3- Before randomization, participants who were born female must be either postmenopausal or permanently sterile, and not intending to conceive by any methods.
- •4- Participant must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study.
排除标准
- •1- Participant has end stage renal disease for which dialysis is required.
- •2- Participant has a contraindication to intramuscular (IM) injections and blood draws example, due to bleeding disorders or a history of difficult blood draws.
- •3- Chronic systemic prophylactic use of antibacterials (including antibiotics and urinary tract antiseptics).
- •Repeated courses administered for recurrent UTIs preceding randomization will not be referred to as chronic.
- •In case of chronic prophylactic use of antibacterials, the last dose must have been administered > 60 days prior to randomization.
- •4- Participant has a history of acute polyneuropathy (for example, Guillain barre syndrome) or chronic inflammatory demyelinating polyneuropathy.
- •5- Participant has received any Escherichia coli (E.
- •coli) or extraintestinal pathogenic Escherichia coli (ExPEC) vaccine.
结局指标
主要结局
1-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
时间窗: Up to 3 years
2-Number of Participants with First IED Event with Microbiological Confirmation in Blood or Other Sterile Sites Caused by ExPEC9V O serotypes
时间窗: Up to 3 years
次要结局
- Number of Participants with First Hospitalized IED Event Caused by ExPEC9V O-serotypes(Up to 3 years)
- Number of Participants with First IED Event Meeting Criteria for Sepsis Caused by ExPEC9V O-serotypes(Up to 3 years)
- Number of Participants with First Bacteremic IED Event Caused by ExPEC9V O-serotypes(Up to 3 years)
- Number of Participants with First Pyelonephritis Event Caused by ExPEC9V O-serotypes(Up to 3 years)
- Number of Participants with First Urinary Tract Infection (UTI) Event Caused by ExPEC9V O-serotypes(Up to 3 years)
- MRU for Acute Bacterial Prostatitis (ABP)(Up to Day 29 Post-ABP)
- Number of Participants with Hospitalization for IED or, UTI, or ABP Events(Up to 3 years)
- Number of Participants with All IEDs (Including Multiple IEDs per Participant) Caused by ExPEC9V O-serotypes(Up to 3 years)
- Number of Participants with All UTIs (Including Multiple UTIs per Participant) Caused by ExPEC9V O-serotypes(Up to 3 years)
- Number of Participants with First IED Event Caused by Any ExPEC O-serotype(Up to 3 years)
- Number of Participants with First Pyelonephritis Event caused By Any ExPEC O-serotype(Up to 3 years)
- Number of Participants with First UTI Event caused by Any ExPEC O-Serotype(Up to 3 years)
- Antibody Titers to Vaccine O-serotype Antigens as Determined by Multiplex Electrochemiluminescent (ECL)-based Immunoassay(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(Up to 3 years)
- Antibody Titers to Vaccine O-serotype Antigens as Determined by Multiplex Opsonophagocytic Assay (MOPA)(Up to 3 years)
- Number of Participants with Solicited Local Adverse Events (AEs)(Up to Day 15 (until 14 days post-vaccination))
- Number of Participants with Solicited Systemic AEs(Up to Day 15 (until 14 days post-vaccination))
- Number of Participants with Unsolicited AEs(Up to Day 30 (until 29 days post-vaccination))
- Number of Participants with Serious Adverse Events (SAEs)(Up to 3 years)
- Short Form-36 (SF-36) Total Scores(Up to 3 years)
- European Quality of Life (EuroQol) 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Scores(Up to 3 years)
- Change from Baseline in Frailty Index(Baseline to 3 years)
- Medical Resource Utilization (MRU) for IED Events(Up to Day 366 Post-IED)
- MRU for UTI Events(Up to Day 29 Post-UTI)
- Length of Stay in Hospital for IED, UTI, or ABP Events(Up to 3 years)
- Number of Participants with IED-related & All-cause Mortality(Up to 3 years)