TY - JOUR
AU - Gaughan, Erin
AU - Quinn, Tom M
AU - Mills, Andrew
AU - Bruce, Annya
AU - Antonelli, Jean
AU - Mackinnon, Alison
AU - Aslanis, Vassilios
AU - Li, Feng
AU - O'Connor, Richard A.
AU - Boz, Cecilia
AU - Mills, Ross
AU - Emanuel, Philip
AU - Burgess, Matthew
AU - Rinaldi, Giulia
AU - Valanciute, Asta
AU - Mills, Bethany
AU - Scholefield, Emma
AU - Hardisty, Gareth
AU - Gwyer Findlay, Emily L
AU - Parker, Richard A
AU - Norrie, John
AU - Dear, James W
AU - Akram, Ahsan R.
AU - Koch, Oliver
AU - Templeton, Kate
AU - Dockrell, David H.
AU - Walsh, Timothy S
AU - Partridge, Stephen
AU - Humphries, Duncan
AU - Wang-jairaj, Jie
AU - Slack, Robert J
AU - Schambye, Hans
AU - Phung, De
AU - Gravelle, Lise
AU - Lindmark, Bertil
AU - Shankar-Hari, Manu
AU - Hirani, Nikhil
AU - Sethi, Tariq
AU - Dhaliwal, Kevin
PY - 2022
DA - August
TI - An Inhaled Galectin-3 Inhibitor in COVID-19 Pneumonitis (DEFINE): A Phase Ib/IIa Randomised Controlled Trial
JO - American Journal of Respiratory and Critical Care Medicine
VL - 207
IS - 2
DO - https://doi.org/10.1164/rccm.202203-0477OC
AB - Rationale: High circulating galectin-3 is associated with poor outcomes in patients with COVID-19. We hypothesised that GB0139, a potent inhaled thiodigalactoside galectin-3 inhibitor with anti-inflammatory and antifibrotic actions, would be safely and effectively delivered in COVID-19 pneumonitis. Objectives: Primary outcomes were safety and tolerability of inhaled GB0139 as an add-on therapy for patients hospitalised with COVID-19 pneumonitis. Methods: We present the findings of two arms of a phase Ib/IIa randomised controlled platform trial in hospitalised patients with confirmed COVID-19 pneumonitis. Patients received standard of care (SoC) or SoC plus 10 mg inhaled GB0139 twice daily for 48 hours, then once daily for up to 14 days or discharge. Results: Data are reported from 41 patients, 20 of which were assigned randomly to receive GB0139. Primary outcomes: the GB0139 group experienced no treatment-related serious adverse events. Incidences of adverse events were similar between treatment arms (40 with GB0139+SoC vs 35 with SoC). Secondary outcomes: plasma GB0139 was measurable in all patients after inhaled exposure, and demonstrated target engagement with decreased circulating galectin (overall treatment effect post-hoc ANCOVA over days 2–7: p=0.0099 vs SoC). Plasma biomarkers associated with inflammation, fibrosis, coagulopathy and major organ function were evaluated. Conclusions: In COVID pneumonitis, inhaled GB013 was well-tolerated, achieved clinically relevant plasma concentrations with target engagement. The data support larger clinical trials to determine clinical efficacy. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT04473053.
PB - ATS journals
UR - https://www.research.ed.ac.uk/en/publications/6c9df868-37b4-4b76-af1a-feb4cdf481f8
KW - Coronavirus (COVID-19)
ER