A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Safety and Efficacy of a Single Dose of ASN100 for the Prevention of Staphylococcus Aureus Pneumonia in Heavily Colonized, Mechanically Ventilated Subjects
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 155
- 试验地点
- 19
- 主要终点
- Efficacy of a Single Intravenous (IV) Dose of ASN100
研究概览
简要总结
The purpose of this study is the prevention of Staphylococcus aureus pneumonia in mechanically ventilated subjects heavily colonized with S. aureus. Staphylococcus aureus is a human pathogenic bacterium that causes severe infections, including pneumonia and sepsis. Hospital-acquired bacterial pneumonia (HABP) caused by S. aureus, including ventilator-associated bacterial pneumonia (VABP) in mechanically ventilated subjects, is a significant public health threat despite efforts to optimize antibiotic treatment. ASN100 is an investigational monoclonal antibody product that targets the toxins produced by S. aureus to protect subjects from developing S. aureus pneumonia.
详细描述
This is a double-blind, randomized, single-dose, placebo-controlled study of ASN100 for the prevention of S. aureus pneumonia in mechanically ventilated subjects who are heavily colonized with S. aureus. This will be a global study conducted at approximately 65 sites to assess the safety, tolerability, and efficacy of ASN100.
Eligible subjects who meet all of the inclusion criteria and none of the exclusion criteria will be screened by semi-quantitative culture of an endotracheal aspirate (ETA) to identify those who are heavily colonized with S. aureus (3+ to 4+). Upon determination of eligibility, subjects will be randomized in a 1:1 ratio to 1 of 2 treatment groups, ASN100 or placebo.
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
- 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
- •Subject is currently hospitalized and is mechanically ventilated endotracheally (i.e., orotracheal or nasotracheal) and, in the Investigator's opinion, will require ongoing ventilator support for at least 48 hours;
排除标准
- •Subject has a chest X-ray or thoracic computed tomography (CT) scan that is definitive for a diagnosis of pneumonia
- •Subject has a known and documented ETA culture showing heavy colonization with a -Gram-negative organism at enrollment or at any time during the Screening period;
- •Significant Neutropenia
- •Severe non-pulmonary source of infection.
- •Subjects with a known history or current (suspected) diagnosis of cytokine release syndrome associated with the administration of peptides, proteins, and/or antibodies.
研究组 & 干预措施
Placebo
Placebo administered as 2 separate intravenous (IV) infusions
干预措施: Placebo (Drug)
ASN100
ASN100 administered as 2 separate intravenous (IV) infusions
干预措施: ASN100 (Drug)
结局指标
主要结局
Efficacy of a Single Intravenous (IV) Dose of ASN100
时间窗: Incidence of S. aureus pneumonia up to but not including Day 22
Percentage of subjects in the MITT population who have or have not developed S. aureus (SA) pneumonia after a single intravenous (IV) dose of ASN100, based on sponsor defined outcome (SDO1). For each arm, the empirical proportion is defined by a ratio, which is the number of SA pneumonia events divided by the total number of subjects in the arm. The inference about the difference of two population rates is based on the empirical counterpart; specifically, the point estimate, 95% confidence interval and p-value for the rate difference. Subjects discontinued from the study due to any cause prior to Day 22 were considered as not developing SA pneumonia for the primary efficacy analysis.
次要结局
- Duration of Mechanical Ventilation(21 days)
- Length of ICU Stay(21 days)
- 28-day All-cause Mortality(28 days)
- ASN-1 and ASN-2 Maximum Serum Concentration (Cmax)(through day 90)
- ASN-1 and ASN-2 Time to Maximum Concentration (Tmax) in Serum(through day 90)
- ASN-1 and ASN-2 Area Under the Concentration-time Curve in Serum(through day 90)
- ASN-1 and ASN-2 Terminal Elimination Half-life (t1/2) in Serum(through day 90)