Source: Annual Congress 2004 - Emphysema and oxygen therapy

Abstract

Background: Individuals with severe alpha 1-antitrypsin (AAT) deficiency (serum levels < 15% of normal) are predisposed to develop progressive, panacinar emphysema. Intravenous administration of plasma-derived AAT may slow disease progression. An alternative source of AAT, combined with a targeted and user-friendly delivery method has been developed. Design: Randomized, double-blinded, placebo-controlled, dose-escalation study of nebulized, yeast-derived, human recombinant AAT (rAAT) in subjects with severe AAT deficiency. A total of 32 subjects were randomized, 8 subjects received placebo and 6 subjects received 1 of 4 rAAT doses [10 mg, 50 mg, 100 mg, or 200 mg nebulizer charge]. Subjects received study drug on Day 1, were re-challenged on Day 15, and were followed for 6 weeks. Outcome: All subjects completed the study. No significant study drug related, clinical or immunological events occurred. Seven non-serious adverse events (AEs) possibly related to study drug occurred: 3 in rAAT-treated subjects and 4 in placebo-treated subjects. Analysis of AEs showed no evidence of involvement of a specific body system. Two serious AEs occurred that were attributable to underlying medical conditions. Conclusion: Nebulized, yeast-derived, human rAAT was safe and well-tolerated in subjects with severe AAT deficiency.

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R. Sandhaus, J. Stocks, J. Stoller, D. Gelmont, D. Sundin, M. Brantly (Denver, Tyler, Cleveland, Westlake Village, Alameda, Gainesville, United States Of America). Phase I safety investigation of an aerosolized, recombinant alpha 1-antitrypsin in subjects with alpha 1-antitrypsin deficiency. Eur Respir J 2004; 24: Suppl. 48, 1509

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