Evaluation of Dupilumab on Airway Inflammation via Mucus Plugging and Lung Imaging in Chronic Obstructive Pulmonary Disease Patients

The primary objective is to evaluate the effect of dupilumab compared to placebo at Week 24 on mucus plugging assessed via high-resolution computed tomography (HRCT) in patients with chronic obstructive pulmonary disease (5). Secondary objectives include:

• Evaluation of mucus volume, airway wall thickness, and airway resistance at Week 24 using HRCT and forced oscillation technique (5).
• Assessment of the safety of dupilumab (4).

This clinical trial involves 252 patients with respiratory tract diseases. The study population includes both male and female individuals within the age ranges categorized as 3 and 4. Participants are characterized by chronic obstructive pulmonary disease, specifically presenting with moderate-to-severe symptoms. Inclusion requires a smoking history of at least 10 pack-years and a post-bronchodilator FEV1/FVC ratio of less than 0.70. Eligible subjects must exhibit a post-bronchodilator FEV1 between 30% and 70% of the predicted value, alongside a Medical Research Council Dyspnea Scale grade of 2 or higher or a COPD assessment test score of at least 10. The population is further defined by GOLD category E classification and evidence of Type 2 inflammation, indicated by specific blood eosinophil counts. Required background treatment includes triple therapy or dual therapy in cases where inhaled corticosteroids are contraindicated. Additionally, participants must present a mucus score of 3 or greater.

This is a randomized, double-blind, placebo-controlled, Phase IV study designed to evaluate the effect of dupilumab on airway inflammation in patients with chronic obstructive pulmonary disease. The investigation focuses on assessing mucus plugging and other lung imaging parameters. Participants will receive either 300 mg of dupilumab via subcutaneous injection or a matched placebo. Background therapy may include salbutamol. The study includes a screening visit to assess eligibility based on smoking history, lung function, and evidence of Type 2 inflammation, such as specific blood eosinophil counts. The primary objective is to measure the change from baseline to Week 24 in the global lung mucus score using UCSF mucus scoring. Secondary endpoints involve assessments via high-resolution computed tomography and the forced oscillation technique to evaluate airway resistance and reactance. The trial duration and participant involvement are structured around these clinical assessments through the end-of-study period.

The experimental treatment consists of dupilumab administered as a solution for injection in pre-filled syringe. The dosage is 300 mg provided via subcutaneous administration.

A matched placebo is utilized as a comparator treatment in this study.

Background therapy involves salbutamol administered through an inhalational route as a pressurised inhalation suspension at a dose of 10 mg.

The primary efficacy endpoint is the change from baseline to Week 24 in the global lung mucus score, as determined by the UCSF mucus scoring method. Secondary efficacy assessments include changes from baseline to Week 24 in mucus volume for the global lung and trimmed distal airway wall thickness at total lung capacity, both evaluated via high-resolution computed tomography (HRCT). Additionally, changes from baseline to Week 24 in airway resistance from R5 to R20 and reactance area are measured using the forced oscillation technique (FOT).