PHASE 2A STUDY OF RPAF AH IN ALLERGEN CHALLENGE IN MILD ASTHMATICS

血小板活化因子(PAF)在哮喘发病机制中具有一定的生物活性。PAF可引起支气管收缩，增加支气管高反应性和血管通透性，刺激呼吸道粘液分泌和嗜酸性粒细胞浸润。PAF的作用受血浆蛋白PAF乙酰水解酶(PAF-AH)的调节，PAF-AH可将PAF水解为生物活性不强的Lyso-PAF。我们发现，重组PAF-AH在人类哮喘小鼠模型中可以抑制PAF诱导的体内炎症。这项2a期研究将评估rPAF-AH作为单剂静脉给药对缓解期、轻度哮喘患者的临床安全性。本研究还将确定rPAF-AH对变应原诱导的早期和晚期哮喘反应的影响。

Platelet-activating factor (PAF) has biologic activities pertinent to asthma pathogenesis. PAF induces bronchoconstriction, increases bronchial hyperreactivity and vascular permeability, and stimulates bronchial mucus secretion and eosinophil infiltration of airways. The actions of PAF are modulated by the plasma protein PAF acetylhydrolase (PAF-AH) that hydrolyzes PAF to biologically inactive lyso-PAF. We have found that recombinant PAF-AH suppresses PAF-induced inflammation in vivo in a murine model of human asthma. This Phase 2a study will evaluate the clinical safety of rPAF-AH, administered intravenously as a single dose to subjects with stable, mild asthma. This study will also determine the effect of rPAF-AH on allergen-induced early and late phase asthmatic responses.