Inhaled Alpha-1 Proteinase Inhibitor Safe, Well-Tolerated and Effective in Raising Sputum Levels in Patients with Cystic Fibrosis

Inhalation of aerosolized alpha-1 proteinase inhibitor (A1PI) permits delivery of drug to the site of active airway disease while limiting systemic exposure, and has been shown to reduce neutrophil elastase burden and inflammation in respiratory secretions of alpha-1 antitrypsin-deficient patients. Utilizing an electronically regulated nebulizer system to deliver the A1PI, Grifols researchers and collaborators at six U.S. academic centers conducted a randomized, double-blind, placebo-controlled Phase IIa study to evaluate the safety of 100 mg or 200 mg of an investigational Alpha-1 Hydrophobic Chromatography Process (Alpha-1 HC) inhaled once daily for three weeks in 30 adult subjects with cystic fibrosis (CF).

Subjects were randomized 2:1 to receive Alpha-1 HC or placebo. Drug delivery was confirmed by a dose-dependent increase in the sputum A1PI. Seven (20%) of 35 adverse events in the 100 mg dose group, three (13%) of 23 in the 200 mg dose group, and four (14.3%) of 28 in the placebo group were drug-related in these subjects. One serious adverse event occurred in one subject within each group. The investigators concluded that Alpha-1 HC was safe and well-tolerated, adding that further studies are needed to determine efficacy and potential use of Alpha-1 HC as chronic therapy in CF lung disease.