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 (rhDNase) 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 study 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

Twelve 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 nonsmokers, and have normal pulmonary function testing. The patients with cystic fibrosis had to have a forced vital capacity greater than 40% predicted normal and have no recent exacerbation (within 2 weeks) of their 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 days 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. Secondary outcome measures were dyspnea score and quantitative bacterial culture.

MAIN RESULTS

Inhalation of rhDNase was well tolerated by all persons. There were no serious adverse reactions, and no allergic reactions were observed, even on rechallenge. No individual developed rhDNase antibodies. Improvement in both lung function and dyspnea score was observed in the adults with cystic fibrosis. Forced vital capacity was 3.2 +/- 0.3 L (mean +/- SE) on day 1 and was 3.5 +/- 0.3 L on day 12. 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 fibrosis and may improve lung function with short-term therapy.