RECOMBINANT HUMAN DNASE INHALATION IN NORMAL SUBJECTS AND PATIENTS WITH CYSTIC-FIBROSIS - A PHASE-1 STUDY

Objective. - To evaluate the safety of recombinant human DNase (rhDNas e) in normal subjects and in patients with cystic fibrosis. Design. - Nonrandomized trial in which individuals inhaled rhDNase three times a day Monday through Friday on two consecutive weeks. Setting. - The st udy was performed in the Clinical Research Center at the University of Washington, Seattle. Patients were recruited from the Cystic Fibrosis Center at the University of Washington. Subjects and Patients. - Twel ve normal subjects and 14 patients with cystic fibrosis were studied ( 12 patients completed the protocol), The subjects and patients had to be aged 18 to 65 years and have a negative pregnancy test, if female. The normal subjects had to have a normal chest roentgenogram, be nonsm okers, and have normal pulmonary function testing. The patients with c ystic fibrosis had to have a forced vital capacity greater than 40% pr edicted normal and have no recent exacerbation (within 2 weeks) of the ir lung infection or change in their medication. Interventions. - The study design was a repetitive dose escalation of aerosolized rhDNase. The subjects inhaled rhDNase three times a day, Monday through Friday, on 2 consecutive weeks and were rechallenged with a single dose 21 da ys after the last dose. Spirometry was measured before and 30 minutes after every rhDNase dose. Main Outcome Measures. - Pulmonary function testing, serum DNase concentrations, and anti-DNase antibodies. Second ary outcome measures were dyspnea score and quantitative bacterial cul ture. Main Results. - Inhalation of rhDNase was well tolerated by all persons. There were no serious adverse reactions, and no allergic reac tions were observed, even on rechallenge. No individual developed rhDN ase antibodies. Improvement in both lung function and dyspnea score wa s observed in the adults with cystic fibrosis. Forced vital capacity w as 3.2 +/- 0.3 L (mean +/- SE) on day 1 and was 3.5 +/- 0.3 L on day 1 2. Forced expiratory volume in 1 second was 2.1 +/- 0.2 L (mean +/- SE ) on day 1 and was 2.3 +/- 0.3 L on day 12. Conclusions. - Aerosolized rhDNase appears safe in normal subjects and in adults with cystic fib rosis and may improve lung function with short-term therapy.