Abstract
OBJECTIVE: To evaluate the safety, tolerability and preliminary efficacy of IBI324, a vascular endothelial growth factor-A/angiopoietin-2 bispecific antibody, in participants with diabetic macular oedema (DME). METHODS AND ANALYSIS: This multicentre, open-label, phase 1 dose-escalation clinical trial consisted of a single ascending dose (SAD) stage and a multiple ascending dose (MAD) stage. 24 participants with fovea-involving DME were enrolled. SAD participants received a single intravitreal injection (IVT) of 0.5 mg, 2 mg or 4 mg IBI324 and were followed up until Day 42 post injection. In the MAD stage, six participants each received 3 monthly IVTs of 2 mg or 4 mg IBI324 and were followed up until determined as 'treatment needed' per prespecified criteria or until 24 weeks after first dose. The primary endpoints were incidence of dose-limiting toxicities (DLTs), adverse events (AEs) and changes in vital signs and laboratory test findings. RESULTS: No DLT, treatment-related AE, AE of special interest or ocular serious AE was reported. Treatment-emergent adverse events (TEAEs), all mild or moderate in severity, were observed in 4 (33.3%) SAD participants and 11 (91.7%) MAD participants. TEAEs of the study eye included intraocular pressure increased, conjunctival haemorrhage, allergic conjunctivitis, posterior capsular opacification and visual acuity decreased. Mean best-corrected visual acuity increase and mean central subfield thickness decrease from baseline in the study eye were observed in all dose groups, accompanied by intraretinal fluid/subretinal fluid improvements. 16 weeks after the last dose, 7 (58.3%) MAD 2 mg and 6 (50.0%) MAD 4 mg participants remained free of 'treatment needed'. CONCLUSION: IBI324 was well tolerated with evidence of functional and anatomical improvement in patients with DME. TRIAL REGISTRATION NUMBER: NCT05489718.