Phase 2b/3 Randomized Double‑Blind Placebo‑Controlled Trial of Lunsekimig in Adults with Inadequately Controlled Eosinophilic COPD

Primary objective: to assess the efficacy of lunsekimig by measuring the annualized rate of moderate to severe COPD exacerbations, a clinically relevant endpoint that reflects disease progression and healthcare utilization in patients with an eosinophilic phenotype. Secondary objectives: • evaluate the effect of lunsekimig on lung function; • assess impact on health‑related quality of life; • determine influence on symptoms and overall disease burden; • examine effect on moderate or severe COPD exacerbations; • characterize the safety profile of lunsekimig; • describe pharmacokinetic parameters; • assess immunogenicity.

The trial enrolled 1,747 participants diagnosed with COPD. Eligible individuals were aged 40 to 80 years, of both sexes, and met defined pulmonary function thresholds (post‑bronchodilator forced expiratory volume in 1 second (FEV1) ≥20 % and ≤70 % of predicted, and FEV1/FVC <0.70). Inclusion required a documented COPD history of at least one year, a body mass index between 18.0 and 40.0 kg/m², and a blood eosinophil count ≥150 cells/μL. Participants were required to be former or current smokers with a smoking history of ≥10 pack‑years and to have experienced ≥2 moderate or ≥1 severe COPD exacerbations in the preceding year. All subjects were receiving triple therapy (inhaled corticosteroid + long‑acting β‑agonist + long‑acting muscarinic antagonist) for a minimum of 12 consecutive weeks and had a Chronic Airways Assessment Test score of ≥10. The cohort, drawn from the broader category of respiratory tract diseases, included vulnerable individuals; selection was based on these clinical and laboratory criteria without additional lifestyle restrictions beyond smoking exposure.

The study is a Phase 2b/Phase 3, multicenter trial evaluating the efficacy and safety of LUNSEKIMIG in adults with inadequately controlled chronic obstructive pulmonary disease (COPD) characterized by an eosinophilic phenotype. Participants meeting defined inclusion criteria will be randomized in a double-blind, placebo-controlled manner to receive either LUNSEKIMIG injection or a matched placebo. The primary objective is to assess the annualized rate of moderate to severe COPD exacerbations, with secondary objectives addressing lung function, health status, and safety outcomes. Recruitment is planned to begin on 2 July 2026 and to end on 22 January 2030. Study visits comprise a screening visit to verify eligibility, a baseline/randomization visit, periodic follow‑up visits for efficacy and safety assessments, and a final end‑of‑study visit. Individual participant involvement extends from the screening visit through the end‑of‑study assessment, with the total duration defined by the protocol. Early termination may be implemented for safety concerns, protocol non‑compliance, or participant withdrawal.

The investigational product, lunsekimig, is supplied as a solution for injection in a pre‑filled syringe. Each syringe contains 00.00 mg of the active substance lunsekimig and is administered by injection according to the study dosing schedule. The route of administration is intramuscular (INJECTION), with dosing frequency defined in the protocol and identical for all participants receiving the test product.

The control arm receives a matched placebo for test, which contains no active pharmaceutical ingredient. The placebo is formulated to be indistinguishable from the active product in appearance, volume, and administration method, and is delivered by the same injection route and schedule as lunsekimig.

All study treatments are administered under double‑blind conditions at designated study visits. Dosing intervals are recorded in the case report form, and adherence is monitored through site‑generated drug accountability logs, inspection of returned syringes, and verification of administration timestamps in the electronic data capture system.

The primary efficacy assessment will be the annualized rate of moderate to severe chronic obstructive pulmonary disease (COPD) exacerbations. This endpoint will be derived from documented exacerbation events occurring throughout the treatment period.

Secondary efficacy evaluations will include:

• Change from baseline in post‑Bronchodilator Forced Expiratory Volume in 1 second (post‑BD FEV1) measured by spirometry.
• Change from baseline in pre‑Bronchodilator Forced Expiratory Volume in 1 second (pre‑BD FEV1) measured by spirometry.
• Change from baseline in the SGRQ‑C total score, a validated health‑related quality‑of‑life questionnaire for COPD.
• Responder analysis for the SGRQ‑C defined as an improvement of ≥4 points.
• Change from baseline in the CAAT score, a chronic airways assessment tool.
• Responder analysis for the CAAT defined as an improvement of ≥2 points.
• Change from baseline in the E‑RS:COPD total score, an electronic symptom diary.
• Responder analysis for the E‑RS:COPD defined as an improvement of ≥2 points.
• Annualized rate of severe COPD exacerbations.
• Time to first moderate or severe COPD exacerbation.
• Time to first severe COPD exacerbation.