NCT05204563已完成3 期
A Multicenter, Randomized, Double-Blind, Comparative, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous Imipenem/Cilastatin/XNW4107 in Comparison With Imipenem/Cilastatin/Relebactam in Adults With Hospital-Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia (EudraCT no. 2022-000081-18) (EUCTR no. 2022-501952-27-00) (IND no. 146614)
Evopoint Biosciences Inc.35 个研究点 分布在 4 个国家目标入组 450 人开始时间: 2022年7月31日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 450
- 试验地点
- 35
- 主要终点
- Day 14 All-cause Mortality Rate
研究概览
简要总结
This study aims to compare treatment with Imipenem/Cilastatin-XNW4107 (IMI-XNW4107) with imipenem/cilastatin/relebactam (IMI/REL) in participants with hospital-acquired or ventilator-associated bacterial pneumonia (HABP or VAPB, respectively). The primary hypothesis is that IMI-XNW4107 is non-inferior to IMI/REL in all-cause mortality.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has HABP or VABP as defined below and requires treatment with IV antibiotic therapy. Fulfills clinical criteria, with onset of criteria occurring after more than 48 hours of hospitalization or within 7 days after discharge from a hospital (for HABP); or at least 48 hours after mechanical ventilation (for VABP)
- •Fulfills clinical criteria with symptoms or signs of cough, expectorated sputum production, dyspnea, worsening oxygenation, increase in respiratory secretions, fever/ hypothermia..
- •Fulfills laboratory test criteria with Leukocytosis/ Leukocytosis/ increase in immature neutrophils
- •Fulfill radiograph criteria with presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia in X-ray/ Chest CT.
- •Female subjects of childbearing potential, who are willing to birth control during the study and for at least 30 days following the last dose of study medication. Male subjects with female sexual partners of childbearing potential are eligible for inclusion if they agree to use birth control for 90 days following the last dose of study medication. Male subjects must agree not to donate sperm
排除标准
- •Gram stain from a respiratory sample shows only Gram-positive cocci.
- •Have known or suspected community-acquired bacterial pneumonia, atypical pneumonia, viral pneumonia including Coronavirus disease, or chemical pneumonia.
- •Have HABP/VABP caused by an obstructive process, including lung cancer or other known obstruction.
- •Have received effective antibacterial drug therapy for the index infection of HABP/VABP for more than 24 hours during the previous 72 hours .
- •Have central nervous system infection.
- •Documented presence of immunodeficiency or an immunocompromised condition
- •Documented or severe hypersensitivity or previous severe adverse drug reaction, especially to any beta-lactam antibiotics, or any of the excipients used in the study drug formulations.
- •History of a seizure disorder requiring ongoing treatment with anti-convulsive therapy or prior treatment with anti-convulsive therapy within the last 3 years.
- •eGFR <15 mL/min/1.73㎡.
- •Patient is receiving hemodialysis or peritoneal dialysis.
- •Anticipated to be treated with any of Valproic acid or divalproex sodium, concomitant systemic Gram-negative antibacterial agents, or concomitant systemic antifungal or antiviral therapy for the index infection of HABP/VABP.
- •Life expectancy is <3 days.
- •Patients in refractory septic shock
- •Patients with 1 or more of laboratory abnormalities in baseline specimens.
- •History of active liver disease or cirrhosis.
- •APACHE II score of >
- •A female who is pregnant or breastfeeding or has a positive pregnancy test at Screening.
研究组 & 干预措施
Imipenem/Cilastatin/XNW4107
Experimental
Imipenem/Cilastatin 500mg/500mg in combination with XNW4107 250mg, Q6h (0.5h Infusion)
干预措施: Combination of Imipenem/Cilastatin and XNW4107 (Drug)
Imipenem/Cilastatin/Relebactam
Active Comparator
Imipenem/Cilastatin/Relebactam 1.25g Q6h (0.5h Infusion)
干预措施: Imipenem/Cilastatin/Relebactam (Drug)
结局指标
主要结局
Day 14 All-cause Mortality Rate
时间窗: Day 14
The all-cause mortality rate at Day 14 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from randomization up to Day 14.
次要结局
- Day 28 All-cause Mortality Rate(Day 28)
- Day 14 and Day 28 All-cause Mortality Rate in the Micro-MITT Population(Day 14, Day 28)
- Day 14 and Day 28 All-cause Mortality Rate in the Extended Micro-MITT(Day 14, Day 28)
- Day 14 and Day 28 All-cause Mortality Rate in the Clinically Evaluable (CE) Population(Day 14, Day 28)
- Day 14 and Day 28 All-cause Mortality Rate in the Microbiologically Evaluable (ME) Population(Day 14, Day 28)
- Day 14 and Day 28 All-cause Mortality Rate in the Carbapenem-resistant MITT (CR-MITT) Population(Day 14, Day 28)
- The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the MITT Population(Day 4, end of treatment (EOT) (up to Day 14), Test-of-Cure (TOC) (Day 21), and Late Follow-up (LFU) (Day 28))
- The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the Micro-MITT Population(Day 4, EOT (up to Day 14), TOC (Day 21), and LFU (Day 28))
- The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the Extended Micro-MITT(Day 4, EOT (up to Day 14), TOC (Day 21), and LFU (Day 28))
- The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the CE Population(Day 4, end of treatment (EOT) (up to Day 14), Test-of-Cure (TOC) (Day 21), and Late Follow-up (LFU) (Day 28))
- The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the ME Population(Day 4, end of treatment (EOT) (up to Day 14), Test-of-Cure (TOC) (Day 21), and Late Follow-up (LFU) (Day 28))
- The Percentage of Participants With Clinical Success as Evaluated by the Investigator in the CR-MITT Population(Day 4, end of treatment (EOT) (up to Day 14), Test-of-Cure (TOC) (Day 21), and Late Follow-up (LFU) (Day 28))
- The Percentage of Participants With Microbiological Success in the Micro-MITT Population(EOT (up to Day 14), TOC (Day 21), and LFU (Day 28))
- The Percentage of Participants With Microbiological Success in the Extended Micro-MITT Population(EOT (up to Day 14), TOC (Day 21), and LFU (Day 28))
- The Percentage of Participants With Microbiological Success in the CR-MITT Population(EOT (up to Day 14), TOC (Day 21), and LFU (Day 28))
- The Percentage of Participants With Microbiological Success in the ME Population(EOT (up to Day 14), TOC (Day 21), and LFU (Day 28))
- The Percentage of Participants With Microbiological Success by Pathogen in the Micro-MITT Population(EOT (up to Day 14), TOC (Day 21), and LFU (Day 28))
- The Percentage of Participants With Microbiological Success by Pathogen in the Extended Micro-MITT Population(EOT (up to Day 14), TOC (Day 21), and LFU (Day 28))
- The Percentage of Participants With Microbiological Success by Pathogen in the ME Population(EOT (up to Day 14), TOC (Day 21), and LFU (Day 28))
- The Percentage of Participants With Microbiological Success by Pathogen in the CR-MITT Population(EOT (up to Day 14), TOC (Day 21), and LFU (Day 28))
- The Percentage of Participants With Overall Success in the Micro-MITT Population(EOT (up to Day 14), TOC (Day 21), and LFU (Day 28))
- The Percentage of Participants With Overall Success in the Extended Micro-MITT Population(EOT (up to Day 14), TOC (Day 21), and LFU (Day 28))
- The Percentage of Participants With Overall Success in the ME Population(EOT (up to Day 14), TOC (Day 21), and LFU (Day 28))
- The Percentage of Participants With Overall Success in the CR-MITT Population(EOT (up to Day 14), TOC (Day 21), and LFU (Day 28))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Day 1 to Day 28)
- Blood XNW4107, Imipenem, and Cilastatin Concentrations(Predose, 5-25 minutes post-dose, and 2-3 hours post-dose on Day 4, 5, or 6)
研究者
研究点 (35)
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