Safety and Tolerability of Recombinant Human Clara Cell 10kDa Protein (rhCC10) Delivered Intratracheally to Premature Neonates With Respiratory Distress Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 22
- 试验地点
- 4
- 主要终点
- Number and type of adverse events
研究概览
简要总结
Bronchopulmonary Dysplasia (BPD) is a multi-factorial disease process that is the end result of an immature, surfactant deficient lung that has been exposed to hyperoxia, mechanical ventilation and infection. These conditions initiate an inflammatory response characterized by elevated inflammatory cell infiltrates and proinflammatory cytokines that lead to the development of significant acute and chronic lung injury.
The study drug, rhCC10, is a recombinant version of natural human CC10 protein. Native CC10 is produced primarily by non-ciliated respiratory epithelial cells, called Clara cells and is the most abundant protein in the mucosal fluids in normal healthy lungs.
The purpose of this study was to evaluate the pharmacokinetics, safety, tolerability and anti-inflammatory effects of a single intratracheal (IT) dose of rhCC10 to intubated premature infants receiving positive pressure ventilation for treatment of respiratory distress syndrome (RDS) to prevent long term respiratory complications referred to as bronchopulmonary dysplasia, and, more recently, as chronic respiratory morbidity (CRM; asthma, cough, wheezing, multiple respiratory infections).
CC10 regulates inflammatory responses and protects the structural integrity of pulmonary tissue while preserving pulmonary mechanical function during various insults (eg. viral infection, bacterial endotoxin, ozone, allergens, hyperoxia). Together these properties suggest that administration of rhCC10 may help to facilitate development of normal airway epithelia and prevent the inflammation that leads to CRM in these infants.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 24 Weeks 至 29 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newborn infants were considered for the study if the following criteria were met:
- •Age < 24 hours;
- •Birthweight between 700 and 1,300 grams;
- •Gestational age greater than or equal to 24 weeks;
- •Diagnosis of neonatal RDS based on clinical and radiographic criteria;
- •Requiring intubation and mechanical ventilation for treatment of RDS;
- •Received at least one dose of surfactant 100 mg/kg (Survanta; Ross Laboratories);
- •Written informed consent from the infant's parent or legal guardian prior to enrollment of the patient and agrees to all study-related procedures and evaluations, including those required after hospital discharge.
排除标准
- •Major congenital abnormalities (chromosomal, genetic, cardiac, pulmonary, or renal);
研究组 & 干预措施
Control
干预措施: placebo (Drug)
High dose rhCC10
5 mg/kg study drug (rhCC10)
干预措施: recombinant human CC10 (rhCC10) (Drug)
Low Dose rhCC10
1.5 mg/kg study drug (rhCC10)
干预措施: recombinant human CC10 (rhCC10) (Drug)
结局指标
主要结局
Number and type of adverse events
时间窗: Adverse events were monitored through 36 wks post-menstrual age (PMA) or hospital discharge
All adverse events were monitored according to the NCI Common Toxicity Criteria. In addition, adverse events specific to, or likely to occur in, premature infants were also monitored, including apnea/bradycardia, sepsis (culture-confirmed), patent ductus arteriosus, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, and necrotizing enterocolitis (NEC).
次要结局
- Assessment of pulmonary inflammatory markers(Days 0-7)
- Total number of days on mechanical ventilation(Through 36 wks postmenstrual age or discharge)
- Hospitalization at 36 weeks PMA(Through 36 wks postmenstrual age or discharge)
- Chronic Respiratory Morbidity(6 & 12 months postmenstrual age)