Author: Quan Dong Nguyen
Co-authors: Sobha Sivaprasad, Chirag Jhaveri, Victor Gonzalez, Raj Maturi, Maged Habib, Andrea Giani, Elizabeth Pearce
AbstractPurpose: Diabetic macular ischemia (DMI) is a common complication of diabetic retinopathy (DR) and can result in irreversible vision loss; DMI currently has no approved treatment. HORNBILL (NCT04424290) is a Phase I/IIa study comprising a non-randomised, open-label, single rising dose (SRD) part and a randomised, sham-controlled, single-masked, multiple-dosing (MD) part. The study is the first to investigate the safety and efficacy of a potential treatment for DMI: the novel intravitreal anti-ischemia modulator BI-X.
Settling/Venue: HORNBILL is a multi-centre trial conducted across 20 sites in Europe and the USA. Eligible patients are those with proliferative DR previously treated using pan-retinal photocoagulation and who have evidence of DMI.
Methods: In the completed SRD part, DMI was defined using optical coherence tomography angiography as any degree of disruption in retinal vascularity within the superficial and/or deep retinal plexus. This definition was refined in the ongoing MD part to a foveal avascular zone (FAZ) size of ≥0.5 mm2 or, failing that, an enlarged perifoveal inter-capillary space in at least one quadrant. The completed SRD part comprised three dosing cohorts: 0.5, 1.0 and 2.5 mg of intravitreal BI-X. The primary SRD endpoint was the number of dose-limiting events. Secondary endpoints included the number of drug-related adverse events (AEs) and ocular AEs. Patients in the ongoing MD part receive either 2.5 mg of intravitreal BI-X (maximum feasible dose established in the SRD part, planned n=20) or a sham injection (planned n=10). The primary MD endpoint is the number of patients with drug-related AEs from drug administration to the end of the study, while secondary endpoints include change from baseline in FAZ size, best-corrected visual acuity (BCVA) and central retinal thickness.
Results: Twelve patients were enrolled in the SRD part, half of whom were male. Their mean age was 61.8 years, with a mean time since reported onset of DMI of 4.8 years. Mean baseline BCVA was 30.8 letters. In total, eight AEs were reported in the SRD part, five of which were ocular and classed as procedure related (conjunctival haemorrhage, ocular hyperaemia, procedural pain, temporary intraocular pressure increase and vitreous detachment) and two of which were classed as ocular but were not procedure related (ocular hyperaemia and vitreous detachment). No dose-limiting events or drug-related AEs were reported. The SRD part identified preliminary signs of efficacy: BCVA improved by 5.3 and 4.0 letters in the 1.0 mg and 2.5 mg groups, respectively. To date, six patients have been enrolled into the MD part.
Conclusions: In the SRD part of HORNBILL, single doses of BI-X were well tolerated by patients with DMI and showed preliminary signs of efficacy. The ongoing MD part is further examining the safety and efficacy of BI-X in patients with DMI.
Disclosures: QDN declares (F) Boehringer Ingelheim, Genentech, Gilead, Regeneron, Santen; (C) Bayer, Regeneron, Santen. SS declares (F) Boehringer Ingelheim, Novartis, Bayer, Allergan, Optos, Opthea, Apellis, Roche; (C) Boehringer Ingelheim, Novartis, Bayer, Allergan, Optos, Heildelberg, Oxurion, Ophtea, Apellis, Roche, Biogen. CJ declares (F) Boehringer Ingelheim, Regenxbio, Genentech, Novartis, Kodiak Science, Gyroscope Therapeutics. VG declares (F) Genentech, Regeneron, Oxurion, Novartis, Alimera, Santen, Iconic Therapeutics, DRCR Net, Boehringer Ingelheim, Insite Vision Inc., Astellas, Chengdu Kanghong Biotechnology Co., Ltd., Opthea, 60° Pharmaceuticals, Apellis, Ribomic USA Inc., Iveric Bio, Inc., Aerie Pharmaceuticals, Occuphire Pharma Inc., Asclepix, Oculis SA, GlaxoSmithKline, Unity Biotechnology, Olatec Therapeutics; (C) Genentech, Regeneron, Oxurion, Novartis, Allergan, Alimera, Valeant, Bausch and Lomb, Santen, Topcon, Beaver-Visitec International, Abbvie, Astellas, Nanoscope Therapeutics, Iridex, Eyevance Pharmaceuticals. RM declares (F) Allegan, Boehringer Ingelheim, Gententech, Gyroscope, NGM Biopharma, Ribomic, Santen, Thrombogenics, Unity Biotechnology; (C) Neurotech and AiViva; (S) Forward Vue Pharma. MH declares (F) Boehringer Ingelheim, Bayer, Alimera; (R) Alimera, Roche, Novartis. AG and LP declare that they are employees of Boehringer Ingelheim.