June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
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
Author Affiliations & Notes
  • Sobha Sivaprasad
    NIHR Moorfields Biomedical Research Centre, London, United Kingdom
  • Quan Dong Nguyen
    Byers Eye Institute, Stanford University School of Medicine, Stanford, California, United States
  • Chirag Jhaveri
    Retina Consultants of Austin, Austin, Texas, United States
    Austin Research Center for Retina, Dell Medical School, Austin, Texas, United States
  • Harsha Sen
    Trinity Research Group, Eye Center South, Dothan, Alabama, United States
  • David M Brown
    Retina Consultants of Texas, Houston, Texas, United States
  • Raj K Maturi
    Midwest Eye Institute, Indianapolis, Indiana, United States
  • Abosede Cole
    Bristol Eye Hospital, Bristol, Bristol, United Kingdom
  • Andrea Giani
    Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany
  • Elizabeth Pearce
    Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany
  • Footnotes
    Commercial Relationships   Sobha Sivaprasad Boehringer Ingelheim, Novartis, Bayer, Allergan, Optos, Heidelberg, Oxurion, Opthea, Apellis, Roche, Biogen, Code C (Consultant/Contractor), Boehringer Ingelheim, Novartis, Bayer, Allergan, Optos, Opthea, Apellis, Roche, Code F (Financial Support); Quan Nguyen Bayer, Regeneron, Santen, Code C (Consultant/Contractor), Boehringer Ingelheim, Genentech, Gilead, Regeneron, Santen, Code F (Financial Support); Chirag Jhaveri Boehringer Ingelheim, Regenxbio, Genentech, Novartis, Kodiak Science, Gyroscope Therapeutics, Code F (Financial Support); Harsha Sen Boehringer Ingelheim, Code F (Financial Support); David Brown Allergan, Apellis, Bayer, Biotime, Gemini, Genentech/Roche, Heidelberg, Novartis, OHR, Optos, Regeneron, Regenxbio, Senju, Zeiss, Code C (Consultant/Contractor), Adverum, Allergan, Apellis, Clearside, Genentech/Roche, Novartis, Opthea, Regeneron, Regenxbio, Samsung, Santen, Code F (Financial Support); Raj Maturi Neurotech, AiViva, Code C (Consultant/Contractor), Allegan, Boehringer Ingelheim, Gententech, Gyroscope, NGM Biopharma, Ribomic, Santen, Thrombogenics, Unity Biotechnology, Code F (Financial Support), Forward Vue Pharma, Code S (non-remunerative); Abosede Cole Novartis UK, Bayer UK, Code R (Recipient); Andrea Giani Boehringer Ingelheim, Code E (Employment); Elizabeth Pearce Boehringer Ingelheim, Code E (Employment)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2308. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Sobha Sivaprasad, Quan Dong Nguyen, Chirag Jhaveri, Harsha Sen, David M Brown, Raj K Maturi, Abosede Cole, Andrea Giani, Elizabeth Pearce; 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. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2308.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

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.


This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.