The purpose of this study is to investigate the effect of alvelestat (an oral neutrophil elastase inhibitor) on blood and sputum biomarkers in patients with PiZZ, null or rare variant phenotype/genotype alpha-1 anti-trypsin deficient lung disease. Change in a number of different blood and sputum biomarkers related to lung damage, inflammation and elastase activity will be measured over a 12 week period. The effect on lung function and respiratory symptoms will also be measured.

Inclusion Criteria:

• Patients with a confirmed diagnosis of alpha-1-anti-trypsin deficiency and a PiZZ, null or other rare geno/phenotype and serum anti-alpha1 antitrypsin levels of less than 11uM
• FEV1 ≥20% predicted
• Computerised tomography (CT) scan evidence of emphysema
• Non-smokers

Exclusion Criteria:

• Primary diagnosis of bronchiectasis
• An ongoing acute exacerbation of the underlying lung disease
• Underlying liver disease or abnormal liver function tests
• Previous augmentation therapy within 6 months of dosing

Double-blind