Efficacy and Safety of Early Depemokimab Initiation as Add-on Therapy in Patients with Chronic Obstructive Pulmonary Disease and Type 2 Inflammation

The primary objective of this study is to evaluate the efficacy of depemokimab compared to placebo in patients with chronic obstructive pulmonary disease characterized by type 2 inflammation. The secondary objectives include the assessment of:

• Additional efficacy endpoints
• Symptoms

This study involves 647 patients consisting of male and female individuals within the age ranges of 18-44 and 45-64 years. The study population is characterized by chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype as determined by blood eosinophil count. Participants must have a documented history of the disease for at least one year, characterized by a post-salbutamol forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio of less than 0.70. Inclusion requires moderate to severe disease severity and an elevated risk for exacerbations, indicated by a history of one moderate event in the previous 12 months alongside specific risk factors such as a modified medical research council (mMRC) dyspnea score of 2 or greater or a COPD assessment test (CAT) score of 15 or greater. The cohort includes current or former smokers with at least 10 pack-years of history. Eligible subjects must have utilized dual or triple inhaler therapy for a minimum of 3 months and maintain a body mass index (BMI) of at least 16 kg/m².

This multicenter, randomized, double-blind, parallel group, placebo-controlled study is designed to evaluate the efficacy and safety of early depemokimab initiation as an add-on treatment in patients with Chronic Obstructive Pulmonary Disease (COPD) exhibiting type 2 inflammation. Participants will be randomized to receive either depemokimab via subcutaneous injection or a placebo consisting of sterile 0.9% (w/v) sodium chloride solution. The primary endpoint is the annualized rate of moderate/severe exacerbations. Secondary endpoints include the time to the first moderate/severe exacerbation and changes from baseline in the Stewardship Questionnaire for Respiratory Quality of Life (SGRQ) total score and the COPD Assessment Test (CAT) at Week 52. The study follows a phase 3A design. Following a screening visit to assess eligibility based on blood eosinophil count, pulmonary function, and exacerbation history, participants will undergo treatment and follow-up assessments. Total participant involvement is subject to the clinical trial duration and specific protocol requirements.

The experimental medication is depemokimab, provided as a solution for injection. The administered dose is 100 mg via subcutaneous injection.

The placebo consists of a sterile 0.9% (w/v) sodium chloride solution supplied in a single-use prefilled syringe.

As background therapy, salbutamol sulfate is administered in the form of inhalation powder. The dose is 800 µg via inhalation.

The primary efficacy endpoint is the annualized rate of moderate/severe exacerbations. Secondary efficacy parameters include the time to first moderate/severe exacerbation and the change from baseline in the SGRQ total score, as measured by the SGRQ-C, at Week 52. Additionally, the change from baseline in the E-RS: COPD total score will be assessed at Week 52.