The Phase I/IIa HORNBILL study: Investigating BI 764524 in patients with diabetic macular ischemia

Abstract

Purpose : Patients with diabetic retinopathy (DR) may develop diabetic macular ischemia (DMI), a complication that can lead to irreversible vision loss. Currently, there is no approved pharmacological treatment for DMI. The two-part HORNBILL study (NCT04424290) is the first clinical trial to investigate a treatment for subjects with proliferative DR previously treated with panretinal photocoagulation and DMI: anti-ischemia modulator BI 764524.

Methods : In the completed single rising dose (SRD) part, 12 subjects received 0.5 (n=3), 1.0 (n=3) or 2.5 mg (n=6) intravitreal BI 764524. The primary SRD endpoint was the number of dose-limiting events; secondary endpoints were the number of drug-related adverse events (AEs) and number of ocular AEs. In the ongoing multiple dosing (MD) part (planned N=30), subjects are receiving three doses of 2.5 mg BI 764524 or sham injection in total over 8 weeks (monthly, with 16 weeks’ follow-up). The primary MD endpoint is the number of subjects with drug-related AEs; secondary endpoints include change from baseline in best-corrected visual acuity (BCVA), foveal avascular zone (FAZ) size and central retinal thickness. DMI was defined in both parts of the study using optical coherence tomography angiography; in the SRD part as any disruption in retinal vascularity in the superficial and/or deep retinal plexus; and in the MD part as FAZ ≥0.5 mm².

Results : No drug-related or dose-limiting AEs were reported in the SRD part. In total, there were eight AEs: five were classed as both ocular and procedure related (conjunctival hemorrhage, ocular hyperemia, procedural pain, temporary intraocular pressure increase and vitreous detachment) and two were classed as ocular but not procedure related (ocular hyperemia and vitreous detachment). Although the SRD part was not powered for efficacy, preliminary signs of improvement in BCVA were observed in the two highest-dose cohorts: +5.3 (1.0 mg) and +4.0 letters (2.5 mg). Recruitment for the MD part has completed; in total, 19 have been assigned to treatment and 10 to sham.

Conclusions : Single doses of BI 764524 were well tolerated and showed potential signs of efficacy. The ongoing MD part is further evaluating the safety and efficacy of BI 764524 in subjects with DMI. The final results are anticipated in April 2023.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.