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
- 已完成
- 入组人数
- 17,797
- 试验地点
- 723
- 主要终点
- Number of Participants with First Invasive Extraintestinal Pathogenic E.coli Disease (IED) Event with Microbiological Confirmation in Blood or Other Sterile Sites Caused by 9-valent Extraintestinal Pathogenic E. coli Vaccine (ExPEC9V) O-serotypes
研究概览
简要总结
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.
详细描述
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 4 years post-vaccination). The total study duration is approximately up to 6 years 9 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
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Placebo
Participants will receive a single IM injection of matching placebo on Day 1.
干预措施: Placebo (Other)
ExPEC9V
Participants will receive a single intramuscular (IM) injection of 9-valent extraintestinal pathogenic Escherichia coli vaccine (ExPEC9V) on Day 1.
干预措施: ExPEC9V (Biological)
结局指标
主要结局
Number of Participants with First Invasive Extraintestinal Pathogenic E.coli Disease (IED) Event with Microbiological Confirmation in Blood or Other Sterile Sites Caused by 9-valent Extraintestinal Pathogenic E. coli Vaccine (ExPEC9V) O-serotypes
时间窗: Up to 4 years
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.
次要结局
- Number of Participants with First IED Event with Microbiological Confirmation in Blood, Other Sterile Sites, or Urine, Caused by ExPEC9V O-serotypes(Up to 4 years)
- Number of All IEDs (Including Multiple IEDs per Participant) Caused by ExPEC9V O-serotypes(Up to 4 years)
- Number of Participants with First Hospitalized IED Event Caused by ExPEC9V O-serotypes(Up to 4 years)
- Number of Participants with First IED Event Meeting Criteria for Sepsis Caused by ExPEC9V O-serotypes(Up to 4 years)
- Number of Participants with First Bacteremic IED Event Caused by ExPEC9V O-serotypes(Up to 4 years)
- Number of Participants with First Pyelonephritis Event Caused by ExPEC9V O-serotypes(Up to 4 years)
- Number of Participants with First Urinary Tract Infection (UTI) Event Caused by ExPEC9V O-serotypes(Up to 3 years)
- Number of 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 Escherichia coli (E.coli)(Up to 4 years)
- Number of Participants with First Pyelonephritis Event caused By E.coli(Up to 4 years)
- Number of Participants with First UTI Event caused by E.coli(Up to 3 years)
- Antibody Titers to Vaccine O-serotype Antigens as Determined by Multiplex Electrochemiluminescent (ECL)-based Immunoassay(Up to 4 years)
- Antibody Titers to Genetically Detoxified Form of Exotoxin A Derived from Pseudomonas Aeruginosa (EPA) as Determined by Multiplex ECL-based Immunoassay(Up to 4 years)
- Antibody Titers to Vaccine O-serotype Antigens as Determined by Multiplex Opsonophagocytic Assay (MOPA)(Up to 4 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 181 days)
- Number of Participants with SAEs Related to Study Vaccine or Study Procedures(Up to 4 years)
- Short Form-36 (SF-36) Total Scores(Up to 4 years)
- European Quality of Life (EuroQol) 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Scores(Up to 4 years)
- Change from Baseline in Frailty Index(Baseline to 4 years)
- Medical Resource Utilization (MRU) for IED Events Caused by ExPEC9V O-Serotype(Up to Day 366 Post-IED)
- MRU for UTI Events Caused by ExPEC9V O-Serotype(Up to Day 29 Post-UTI)
- MRU for Acute Bacterial Prostatitis (ABP) Events Caused by ExPEC9V O-Serotype(Up to Day 29 Post-ABP)
- Number of Participants with the Hospitalization for IED or, UTI, or ABP Events Caused by ExPEC9V O-Serotype(Up to 4 years)
- Length of Stay in Hospital for IED, UTI, or ABP Events Caused by ExPEC9V O-Serotype(Up to 4 years)
- Number of Participants with the Intensive Care Unit (ICU) Hospitalization for IED or UTI or ABP Events Caused by ExPEC9V O-Serotype(Up to 3 months post clinical event)
- Length of ICU Stay in Hospital for IED, UTI, or ABP Events Caused by ExPEC9V O-Serotype(Up to 3 months post clinical event)
- Number of Participants with IED-related and All-cause Mortality(Up to 4 years)