Study Design and Patient Population

This multicenter, double-blind, placebo-controlled, study was conducted between November 28, 2017, and January 10, 2019. Eligible patients were aged 40–80 years, had a ≥10 pack-year smoking history and an established history of COPD and were experiencing an acute moderate or severe (hospitalized) COPD exacerbation requiring standard-of-care treatment, defined as prescription of systemic corticosteroids (prednisone 40 mg/day or equivalent) for 5 days and antibiotics for 7 days. Patients were randomly assigned to 12 weeks treatment with placebo, or nemiralisib 12.5 µg, 50 µg, 100 µg, 250 µg, 500 µg, or 750 µg, administered once daily via the ELLIPTA dry powder inhaler (ratio of 3:1:1:1:1:1:3, stratified by exacerbation severity, moderate or severe), followed by an exploratory 12-week follow-up period (Supplementary Materials, Figure S1). Nemiralisib was formulated as a lactose/magnesium stearate (0.4%) blend, with small variations in lactose content with increasing doses of nemiralisib, which were not anticipated to impact aerodynamic performance. Note, the 12.5 µg dose was introduced to the study following a protocol amendment, and so the sample size of this group was small. Randomization was centralized via web-based Interactive Response Technology and the first dose of randomized treatment was required to be no later than 48 h after diagnosis and the start of standard-of-care treatment. Patients could continue their regular maintenance COPD treatment during the study and this could be modified at the investigator’s discretion.

Written informed consent was obtained from each patient prior to any study-specific procedures. The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the relevant ethics committee/institutional review boards and regulatory authorities according to individual country requirements (details given in Supplementary Materials, Appendix 1).

Further details on the eligibility criteria can be found on www.clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT03345407","term_id":"NCT03345407"}}NCT03345407.