NCT04322929

Roflumilast in Non-CF Bronchiectasis Study (2019)

Completed Phase 2 Last updated 9 December 2024

What this trial tests

Phase 2 trial testing Roflumilast Oral Tablet in Non-cystic Fibrosis Bronchiectasis in 42 participants. Completed in 30 November 2024.

Timeline

12 November 2020

Primary endpoint
30 June 2024

30 November 2024

Quick facts

Lead sponsor	The University of Hong Kong
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	42
Start date	12 November 2020
Primary completion	30 June 2024
Estimated completion	30 November 2024
Sites	1 location across Hong Kong

Drugs / interventions tested

• Roflumilast Oral Tablet

Conditions studied

• Non-cystic Fibrosis Bronchiectasis — all drugs for Non-cystic Fibrosis Bronchiectasis →

Sponsor

The University of Hong Kong

Who can join

18 and older, any sex, with Non-cystic Fibrosis Bronchiectasis. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Clinical Implication of Phosphodiesterase-4-Inhibition.
   Schick MA, Schlegel N. · · 2022 · cited 56× · PMID 35163131 · DOI 10.3390/ijms23031209
2. Exacerbation Prevention and Management of Bronchiectasis.
   Choi JY. · · 2023 · cited 6× · PMID 37165624 · DOI 10.4046/trd.2023.0010
3. Therapies for bronchiectasis: mechanisms and potential effects.
   Yu L, Zhu HR, Jin XH, Ding J, et al · · 2026 · PMID 41789076 · DOI 10.3389/fimmu.2026.1735598