Author: Sobha Sivaprasad (United Kingdom)
Co-authors: Harsha Sen, Raj Maturi, Yasir Sepah, Abosede Cole, Quan Dong Nguyen, Victor Chong
Purpose
Diabetic macular ischemia (DMI) is a common complication of diabetic retinopathy (DR) that can lead to irreversible vision loss. Currently, there is no approved treatment for DMI. HORNBILL (NCT04424290) is an ongoing Phase I/IIa study investigating the safety, tolerability and early biological response of the intravitreal ischemia modulator agent BI-X in patients with DMI, in stable treated eyes with proliferative diabetic retinopathy (PDR).
Setting/Venue
In the non-randomised, open-label, single rising dose (SRD) phase of the study, 9 patients have been enrolled, with 3 more to be recruited. In the randomised, sham-controlled multiple dosing (MD) phase of the study, a further 30 patients will be enrolled and followed for 22 weeks.
Methods
Patients with PDR previously treated with pan-retinal photocoagulation (PRP) and evidence of DMI are eligible for study inclusion. In the SRD part, DMI is defined (using optical coherence tomography angiography [OCTA]) as the presence of any degree of disruption in retinal vascularity within the superficial and/or deep retinal plexus. In the MD part, DMI is defined (using OCTA) as a foveal avascular zone of ≥0.5 mm2. To date, 9 patients have enrolled in three SRD cohorts in the SRD part of the study (0.5, 1.0 and 2.5 mg of BI-X; 3 per cohort), with 3 further patients planned in the 2.5 mg cohort. Each patient received one intravitreal dose of BI-X. The primary endpoint is the number of dose-limiting events. Secondary endpoints include the numbers of drug-related and ocular adverse events (AEs).
Results
The mean age of patients in the SRD part was 60.9 (standard deviation ±9.1) years, and most were Caucasian (66.7%). Mean % baseline HbA1c was similar between groups (0.5 mg: 8.1; 1.0 mg: 8.0; 2.5 mg: 9.3). Mean baseline best-corrected visual acuity (BCVA) varied between cohorts and was lowest in the 0.5 mg cohort (0.5 mg: 8.3; 1.0 mg: 52.7; 2.5 mg: 40.7). No dose-limiting events or drug-related AEs were reported. Overall, 6 AEs were reported, none of which were severe. Two ocular AEs were reported in the 0.5 mg cohort (conjunctival haemorrhage and ocular hyperaemia). Three procedure-related AEs were reported. One patient (0.5 mg) had a conjunctival haemorrhage that resolved without sequelae. A second patient (0.5 mg) with glaucoma experienced a temporary increase in intraocular pressure (IOP) but reported no pain or discomfort and was treated with topical anti-glaucoma therapies, after which IOP reduced. The third patient (2.5 mg) experienced mild post-procedural pain. To date, the 0.5 and 1.0 mg cohorts have completed 57 days’ follow-up, with a reported increase in mean BCVA (0.5 mg: 8.3 to 9.0; 1.0 mg: 52.7 to 54.3).
Conlusions
In the SRD part of the HORNBILL study, single rising doses of BI-X were well tolerated by patients with DMI, with no dose-limiting events, severe AEs or drug-related AEs reported to date. There was also an increase in mean BCVA at 57-day follow-up. The effect of 2.5 mg BI-X on BCVA and foveal avascular zone size in patients with DMI will be further examined in the second part of this study through a sham-controlled, single-masked, randomised, MD cohort.
Financial Disclosure
Sobha Sivaprasad: Personal Financial Interest: BI, Novartis, Bayer, Allergan, Optos, Opthea, Apellis, Roche. Consultant: BI, Novartis, Bayer, Allergan, Optos, Heidelberg, Oxurion, Opthea, Apellis, Roche, Biogen.
Comments
Additional Co-authors: 7. Louis-Josef Bour - Boehringer Ingelheim International GmbH, Germany 8. Elizabeth Pearce - Boehringer Ingelheim International GmbH, Germany
