Roflumilast in Non-CF Bronchiectasis Study
Roflumilast Oral Tablet · Phase 2
About this trial
This is a single-arm, open label, Phase II study of 12-week use of Roflumilast in stable-state non-cystic fibrosis bronchiectasis subjects. Bronchiectasis refers to a suppurative lung condition characterized by pathological dilatation of bronchi. The predominant aetiology of bronchiectasis in the Western population is related to cystic fibrosis (CF), which is genetically determined. Bronchiectasis due to other causes are generally grouped under the term "non-CF bronchiectasis", which accounts for practically all cases that are seen commonly in Hong Kong and many other Chinese populations. The main pathogenesis of non-CF bronchiectasis involves airway inflammation, abnormal mucus clearance and bacterial colonization, resulting in progressive airway destruction and distortion. This destructive process perpetuates in a vicious circle even when the initial insult has subsided, which is commonly due to an infective process like tuberculosis in Hong Kong. Patients with extensive bronchiectasis present with chronic cough, copious purulent sputum, haemoptysis, progressive lung function loss, and episodes of infective exacerbations. The current treatment strategies mainly focus on targeting the key elements in the pathogenesis of non-CF bronchiectasis. Apart from regular chest physiotherapy and postural drainage to help clearing mucus from bronchiectatic airways, inhalational and parenteral antibiotics have also been used to reduce the bacterial load in destroyed airways, thus controlling and preventing infective exacerbations. In recent years, accumulated evidence has suggested a central role of airway inflammation and immune dysregulation in the evolution of non-CF bronchiectasis. Chronic obstructive pulmonary disease (COPD) is a progressive destructive process on exposure to noxious environmental agents (e.g. tobacco smoke) that affects both the airways (chronic bronchitis) and lung parenchyma (emphysema), leading to loss of lung function and exercise capacity. Both COPD and bronchiectasis share similarities in clinical presentation and pathogenetic mechanisms. Neutrophilic inflammation and bacterial colonization are also the cornerstone in the airways of patients with COPD. Roflumilast, a phosphodiesterase 4 (PDE4) inhibitor, has demonstrated anti-inflammatory activity in COPD resulting in reduction in exacerbation frequency. This is the first-in-class and the only one clinically available PDE4 inhibitor that is approved worldwide (including Hong Kong) for treatment of severe COPD with frequent exacerbations. At the time of writing, the exact role and clinical evidence for roflumilast in dampening airway inflammation in non-CF bronchiectasis is still lacking. Given the common pathogenetic mechanism via neutrophilic inflammation between non-CF bronchiectasis and COPD, as well as the robust clinical activity of roflumilast in COPD, this study is designed to provide initial scientific evidence on the activity of roflumilast on neutrophilic airway inflammation in patients with stable-state non-CF bronchiectasis. This study aims to investigate the effect of 12-week treatment with roflumilast on neutrophilic airway inflammation in stable-state non-CF bronchiectasis.