Study design of a Phase III study (AIRTIVITY) of the novel dipeptidyl peptidase 1 (cathepsin C) inhibitor verducatib in people with bronchiectasis

Bronchiectasis (BE) is a chronic lung disease characterised by neutrophilic inflammation, where neutrophil serine proteases (NSPs) overwhelm antiproteases, impairing the NSP–antiprotease balance. Chronic inflammation and infection, impaired mucociliary clearance, and progressive structural lung damage contribute to a vicious vortex that leads to pulmonary exacerbations (PExs) and disease progression. NSPs are activated by dipeptidyl peptidase 1 (DPP1, or cathepsin C). Therefore, DPP1 inhibition reduces active NSPs in circulating neutrophils, restoring the NSP–antiprotease balance in the airways of people with BE. In the Phase II AIRLEAF study, the DPP1 inhibitor verducatib (BI 1291583) reduced PEx risk in adults with BE. Here, we outline the design of a Phase III study (AIRTIVITY) assessing the efficacy, safety, and tolerability of verducatib in people with BE. AIRTIVITY is a randomised, double-blind, placebo-controlled study that will include ~1,680 adults with BE of various aetiologies to receive verducatib 2.5 mg or placebo (2:1) for 52 to 76 weeks ([ Fig. 1 ]). Participants must be≥18 years old and have computed tomography-confirmed BE and with a history of PEx requiring antibiotic treatment (≥2 PEx in the past year or≥1 PEx in the past year plus St. George’s Respiratory Questionnaire symptoms score>40 at screening). The safety of verducatib will be monitored through clinical assessment, adverse event reporting and monitoring of safety laboratory parameters. The primary objective of AIRTIVITY is to evaluate verducatib 2.5 mg compared with placebo based on the primary endpoint: the annualised rate of PExs up to Week 76. The main secondary endpoints at Week 52 are lung function changes from baseline (forced expiratory volume in 1 second and forced vital capacity) and change from baseline in Quality of Life-Bronchiectasis respiratory symptoms score. Up to Week 76, the main secondary endpoints are time to first PEx and rate of severe PExs. Additional exploratory assessments focus on modifying effects meaningful to people with BE. The intent of AIRTIVITY is to further evaluate evidence of the efficacy, safety and tolerability of verducatib in a large and broad population of people with BE. Study recruitment began in Q2 of 2025. Fig. 1 Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany