PMID- 35978329
OWN - NLM
STAT- MEDLINE
DCOM- 20220819
LR  - 20221012
IS  - 1745-6215 (Electronic)
IS  - 1745-6215 (Linking)
VI  - 23
IP  - 1
DP  - 2022 Aug 17
TI  - HORNBILL: a phase I/IIa trial examining the safety, tolerability and early 
      response of BI 764524 in patients with diabetic retinopathy and diabetic macular 
      ischaemia-rationale, study design and protocol.
PG  - 669
LID - 10.1186/s13063-022-06527-y [doi]
LID - 669
AB  - BACKGROUND: Diabetic macular ischaemia (DMI) is a complication of diabetic 
      retinopathy that leads to irreversible vision loss. DMI is characterised by 
      reduced retinal vessel density and enlargement of the foveal avascular zone 
      (FAZ). Despite its clinical burden, there is no formal consensus on the 
      definition of DMI, and no approved treatment. Semaphorin 3A (Sema3A) is an axonal 
      guidance molecule that blocks revascularisation of the ischaemic retina. Sema3A 
      modulation is therefore a promising mechanism of action for the treatment of 
      ischaemic eye diseases. BI 764524 is an intravitreal anti-Sema3A ischaemia 
      modulator agent. METHODS: HORNBILL (NCT04424290) is a phase I/IIa trial 
      comprising a non-randomised, open-label, single rising dose (SRD) part and a 
      randomised, masked, sham-controlled multiple dose (MD) part to investigate the 
      safety, tolerability and early biological response of ischaemia modulator BI 
      764524 in adults (>/=18 years) with DMI. DMI will be defined using optical 
      coherence tomography angiography (OCTA) as either any degree of disruption in the 
      retinal vascularity (SRD) or a FAZ of >/=0.5 mm(2) (MD). Subjects in the SRD part 
      will receive 0.5, 1.0 or 2.5 mg of BI 764524; the maximum tolerated dose will 
      then be used in the MD part. A minimum of 12 subjects will be enrolled into the 
      SRD part; planned enrollment is 30 for the MD part. The primary endpoint of the 
      SRD part is the number of subjects with dose-limiting adverse events (AEs) until 
      day 8. The primary endpoint of the MD part is the number of subjects with 
      drug-related AEs from baseline to end of study, and secondary endpoints include 
      change from baseline in the size of the FAZ, best-corrected visual acuity and 
      central retinal thickness. DISCUSSION: DMI is a poorly defined condition with no 
      treatment options. HORNBILL is the first clinical trial to assess a treatment for 
      DMI and to use OCTA as a means to define and examine DMI. The OCTA data generated 
      in this trial could form the basis of formal diagnostic criteria for DMI. 
      Furthermore, the novel mechanism of action (Sema3A modulation) explored in this 
      trial has the potential to revolutionise the treatment landscape for patients 
      with DMI. TRIAL REGISTRATION: ClinicalTrials.gov NCT04424290 ; EudraCT 
      2019-004432-28. Registered on 9 June 2020.
CI  - (c) 2022. The Author(s).
FAU - Chong, Victor
AU  - Chong V
AUID- ORCID: 0000-0002-7693-522X
AD  - UCL Institute of Ophthalmology, University College London, London, UK. 
      victor@eretina.org.
FAU - Nguyen, Quan Dong
AU  - Nguyen QD
AD  - Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA.
FAU - Sepah, Yasir
AU  - Sepah Y
AD  - Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA.
FAU - Giani, Andrea
AU  - Giani A
AD  - Boehringer Ingelheim International GmbH, Ingelheim, Germany.
FAU - Pearce, Elizabeth
AU  - Pearce E
AD  - Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT04424290
GR  - P30 EY026877/EY/NEI NIH HHS/United States
PT  - Clinical Trial Protocol
PT  - Journal Article
DEP - 20220817
PL  - England
TA  - Trials
JT  - Trials
JID - 101263253
SB  - IM
MH  - Adult
MH  - Clinical Trials, Phase I as Topic
MH  - Clinical Trials, Phase II as Topic
MH  - *Diabetes Mellitus
MH  - *Diabetic Retinopathy/diagnosis/drug therapy
MH  - Fluorescein Angiography/methods
MH  - Humans
MH  - Ischemia/drug therapy
MH  - *Macula Lutea/blood supply
MH  - Randomized Controlled Trials as Topic
MH  - Tomography, Optical Coherence/methods
MH  - Visual Acuity
PMC - PMC9386971
OTO - NOTNLM
OT  - Clinical trial
OT  - Diabetic macular ischaemia
OT  - Diabetic retinopathy
OT  - HORNBILL
OT  - OCT
OT  - OCTA
COIS- VC declares that he is an employee of Janssen R&D LLC, but that this work was 
      performed prior to Janssen employment and is not endorsed by Janssen; at the time 
      of project initiation, he was an employee of Boehringer Ingelheim. QDN declares 
      funding from Boehringer Ingelheim, Genentech, Gilead, Regeneron and Santen and 
      consulting for AsclepiX, Bayer, Regeneron and Santen. YS declares financial 
      support from Boehringer Ingelheim. AG and EP declare that they are employees of 
      Boehringer Ingelheim.
EDAT- 2022/08/18 06:00
MHDA- 2022/08/20 06:00
PMCR- 2022/08/17
CRDT- 2022/08/17 23:46
PHST- 2021/12/14 00:00 [received]
PHST- 2022/07/06 00:00 [accepted]
PHST- 2022/08/17 23:46 [entrez]
PHST- 2022/08/18 06:00 [pubmed]
PHST- 2022/08/20 06:00 [medline]
PHST- 2022/08/17 00:00 [pmc-release]
AID - 10.1186/s13063-022-06527-y [pii]
AID - 6527 [pii]
AID - 10.1186/s13063-022-06527-y [doi]
PST - epublish
SO  - Trials. 2022 Aug 17;23(1):669. doi: 10.1186/s13063-022-06527-y.