Randomised, Multicentre, Double-blind, Placebo-controlled Study to Assess the Safety, Efficacy and Pharmacodynamics After the Intravenous Administration of CAL02 in Severe Community-acquired Pneumonia Due to Streptococcus Pneumoniae
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Combioxin SA
- 入组人数
- 19
- 试验地点
- 10
- 主要终点
- Frequency, severity and characteristics of adverse events after two iv. administrations of CAL02.
研究概览
简要总结
The objectives of this study are to assess the safety, tolerability, clinical and microbiological efficacy and pharmacodynamics of patients who have severe pneumonia caused by Streptococcus pneumoniae after the intravenous administration of CAL02 in addition of standard of care antibiotic treatment.
详细描述
Streptococcus pneumoniae is the most frequently identified pathogen of community-acquired bacterial pneumonia and its severe forms are associated with high morbidity and mortality, despite pneumococcal vaccines and medical treatment (antibiotic therapy, alone or in combination). Bacterial toxins, such as the pore-forming toxin (PFT) pneumolysin (from Streptococcus pneumoniae), are involved in the development of invasive disease and play a key role in severe and fatal complications. CAL02 offers a novel therapeutic approach by neutralising bacterial toxins, such as pneumolysin, which recognise specific microdomains on host cell membranes, called lipid rafts.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult male or female patients ≥ 18 years and ≤ 80 years of age
- •Body weight 40-140 kg
- •Severe pneumonia caused by Streptococcus pneumoniae managed in an ICU
- •CURB-65 score ≥ 3 in patients aged > 65 and CURB-65 ≥ 2 in patients aged < 65
- •Streptococcus pneumoniae identification with the urine antigen test or any other proven documented identification method
- •Written informed consent provided by the patient, the relatives or the designated trusted person and/or according to local guidelines
排除标准
- •Patients with hospital-acquired-, health care-acquired- or ventilator- associated-pneumonia
- •More than (i) 12 hours since diagnosis of severe CAPP and (ii) 24 hours or 60 hours since antibiotic treatment IV or per os, respectively, unless documented not to be active against S. pneumoniae, will have elapsed at the time of IMP administration
- •APACHE II score > 30 points
- •SOFA score > 12 points
- •Inability to maintain a mean arterial pressure ≥ 50 mm Hg
- •Known hypersensitivity to liposomal formulations
- •Patients with severe neutropenia or lymphoma or current or anticipated chemotherapy
- •End-stage neuromuscular disorders
- •Patients who have long-term tracheostomy
- •Current or recent participation in an investigational study
- •Presence of other pneumococcal site infection
- •Patients with known acquired immune deficiency syndrome (AIDS) with CD4 count < 200 cells/mL
- •Patients with known post-obstructive pneumonia (active primary lung cancer or another malignancy metastatic to the lungs)
- •Patients with cystic fibrosis, Pneumocystis jiroveci pneumonia, or active tuberculosis
- •Patients receiving immunosuppressant therapy
- •Patients with a known liver function deficiency
- •Splenectomised patients
- •Patients who have experienced an allergic reaction to eggs
- •Moribund clinical condition
- •Nursing and pregnant women
- •Women of child bearing potential not using an effective contraception.
研究组 & 干预措施
CAL02 Low-dose
Liposomal formulation
干预措施: CAL02 Low-dose (Drug)
CAL02 High-dose
Liposomal formulation
干预措施: CAL02 High-dose (Drug)
Placebo
Saline
干预措施: Placebo (Drug)
结局指标
主要结局
Frequency, severity and characteristics of adverse events after two iv. administrations of CAL02.
时间窗: 29 days
To determine the safety profile of CAL02
次要结局
- Clinical efficacy: cure.(29 days.)
- Pharmacodynamic effects.(29 days.)
- Survival.(29 days)
- Microbiological efficacy.(29 days.)