A Phase I/IIa trial examining the safety and efficacy of BI-X in patients with diabetic macular ischemia and diabetic retinopathy: The HORNBILL study

Abstract

Purpose : Diabetic macular ischemia (DMI) is a complication of diabetic retinopathy (DR) that can result in irreversible vision loss. There is no approved treatment for DMI. The non-randomized, open-label, single rising dose (SRD)/multiple dosing (MD) HORNBILL study (NCT04424290) is investigating the safety and efficacy of intravitreal BI-X, an anti-ischemia modulator, in patients with DMI.

Methods : Patients with DR treated with pan-retinal photocoagulation who have evidence of DMI are eligible for inclusion in both parts of the study, defined (using optical coherence tomography angiography) in the completed SRD part as any degree of disruption in retinal vascularity within the superficial and/or deep retinal plexus, and in the ongoing MD part as a foveal avascular zone (FAZ) size of ≥0.5 mm². The SRD part comprised three dosing cohorts (0.5, 1.0, and 2.5 mg of BI-X), and the primary endpoint was the number of dose-limiting events; secondary endpoints were the number of drug-related adverse events (AEs) and number of ocular AEs. The primary MD endpoint is the number of patients with drug-related AEs; secondary endpoints include change from baseline of best-corrected visual acuity (BCVA), FAZ size, and central retinal thickness.

Results : The SRD part enrolled 12 patients. Half of the patients were female, and the mean age was 61.8 years. The mean time since reported onset of DMI was 4.8 years, and mean BCVA was 30.8 letters. In total, 8 AEs were reported; 5 were ocular (conjunctival hemorrhage, ocular hyperemia, procedural pain, temporary intraocular pressure increase, vitreous detachment), all of which were deemed procedure-related other than hyperemia and vitreous detachment. There were no dose-limiting events, or drug-related AEs reported. Preliminary signs of efficacy were observed; BCVA improved by 5.3 and 4.0 letters in the 1.0 mg and 2.5 mg groups, respectively. The maximum feasible dose in the SRD part was 2.5 mg, which is now being used in the ongoing MD cohort, into which two patients have been enrolled.

Conclusions : Single doses of BI-X were well tolerated by patients with DMI, with no dose-limiting events or drug-related AEs reported. The ongoing single-masked, randomized, MD study will further examine the efficacy of BI-X in patients with DMI.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.