An Inhaled Galectin-3 Inhibitor in COVID-19 Pneumonitis (DEFINE): A Phase Ib/IIa Randomised Controlled Trial.

ABSTRACT

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. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http//creativecommons.org/licenses/by-nc-nd/4.0/).