Abstract
Background Alpha-1-Antitrypsin (AAT) deficient individuals have a greater risk for developing chronic obstructive pulmonary disease than individuals with normal AAT levels.
Methods A double-blind randomised parallel group, placebo-controlled trial to examine the safety and tolerability of “Kamada-AAT for Inhalation” (inhaled AAT) in subjects with AAT deficiency, and to explore its effect on AAT and biomarkers in the lung epithelial lining fluid (ELF). Thirty-six patients with severe AAT deficiency were randomised 2:1 to receive 80 mg or 160 mg inhaled AAT or placebo once daily for 12 weeks. The primary outcomes were AAT and anti-neutrophil elastase capacity (ANEC) in bronchoalveolar lavage (BAL) and plasma after treatment. Secondary outcomes included safety, levels of normal M-type AAT in the plasma, and concentrations of AAT, neutrophil elastase (NE), AAT-NE complexes, and neutrophil count in the ELF.
Results Twelve weeks of active treatment significantly increased AAT, ANEC and AAT-NE complexes in the ELF. Mean antigenic AAT levels in the ELF were restored to 5.2±2.3 μM in the 80 mg arm and to 17.7±2 μM in the 160 mg arm. Both doses significantly restored AAT anti-protease activity within the lung and reduced NE levels. M-specific AAT levels in plasma increased in a dose dependent manner. A clinically meaningful reduction in ELF neutrophil % was observed in the 80 mg arm. AAT for inhalation was well tolerated.
Conclusions Inhaled AAT restores protease anti-protease homeostasis and may represent a safe and effective therapy
Footnotes
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Conflict of interest: Naveh Tov and Noga Alagem are Kamada employees. All other authors have no conflict of interest to declare.
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- Received May 25, 2024.
- Accepted July 20, 2024.
- Copyright ©The authors 2024
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