Alpha 1-Antitrypsin Deficiency, COPD, Emphysema
Conditions
Keywords
PiZZ or Null, Neutrophil elastase inhibitor, Alpha-1, Alvelestat, AZD9668, MPH966, Rare variant genotype, Astraeus, AATD, Alpha 1-Antitrypsin Deficiency, Lung Disease
Brief summary
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.
Interventions
DRUGPlacebo Oral Tablet
twice daily administration
DRUGAlvelestat oral tablet - dose 1
twice daily administration
DRUGAlvelestat oral tablet - dose 2
twice daily administration
Sponsors
Syneos Health
Mereo BioPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
placebo-controlled, dose ascending, sequential group
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline on blood biomarkers of neutrophil elastase activity compared to baseline and placebo | 12 weeks | Within-individual change from baseline up to end of treatment in: * Blood neutrophil elastase activity * Blood Aα-Val 360 levels * Plasma desmosine/isodesmosine levels |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline on other blood biomarkers of neutrophil elastase activity | 12 weeks | Frequency of neutrophil elastase levels below the limit of detection from baseline to end of treatment |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in St. George's Respiratory Questionnaire (SGRQ-C) to end of treatment | 12 weeks | Total score |
| Change from baseline in pulmonary function | 12 weeks | Change from baseline in forced expiratory volume in 1 second (FEV1) |
Countries
Belgium, Canada, Denmark, Poland, Spain, Sweden, United Kingdom, United States
Outcome results
None listed