HORNBILL: A Study to Test Different Doses of BI 764524 in Patients Who Have Had Laser Treatment for a Type of Diabetic Eye Disease Called Diabetic Retinopathy With Diabetic Macular Ischemia

Study Overview
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Brief Summary
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This is a study in people with a type of diabetic eye disease called diabetic retinopathy with diabetic macular ischemia. People who have had laser treatment for their diabetic retinopathy can participate in the study. The laser treatment is called panretinal photocoagulation. The purpose of the study is to find out how well different doses of a medicine called BI 764524 are tolerated. BI 764524 is injected into the eye. The study has 2 parts. In the first part, participants get different doses of BI 764524 only once. Participants are in the first part for about 5 months and visit the study site about 8 times. In the second part, participants are put into different groups by chance. Some participants get BI 764524 injections every 4 weeks. Other participants get sham injections every 4 weeks. A sham injection means that it is not a real injection and contains no medicine. Participants cannot tell whether they get the real injection or a sham injection. For the second part, participants are in the study for about 7 months. During this time, they visit the study site about 7 times. In this study, BI 764524 is given to humans for the first time. The doctors compare how well people tolerate the BI 764524 injections and the sham injections. The doctors also regularly check the general health of the participants.

Official Title
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A First-in Human Trial to Study Safety and Tolerability of Single Rising Intravitreal dOses (Open Label, Non-randomized, Uncontrolled) and in Addition the Early Biological Response of Multiple intravitReal Dosing (Single-masked, raNdomized, Sham-controlled) of BI 764524 in panretinaL Photocoagulation (PRP) Treated proLiferative Diabetic Retinopathy (PDR) Patients With Diabetic Macular Ischemia (DMI) - the HORNBILL Study

Conditions
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Diabetic Retinopathy

Intervention / Treatment
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* Drug: BI 764524
* Drug: Sham control of BI 764524


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Single rising dose (SRD) and multiple dosing (MD) part: Pan-retinal photo coagulation treated proliferative diabetic retinopathy (PDR) participants with either no or inactive retinal neovascularization per investigator judgement in the study eye Male or female participants of age ≥ 18 years HbA1c of ≤ 12.0% Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use two methods of contraception with at least one of them being a highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information and in the clinical trial protocol. --A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Tubal ligation is NOT a method of permanent sterilisation. A postmenopausal state is defined as no menses for 2 years without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 2 years of menorrhea, a single FSH measurement is sufficient. Signed and dated written informed consent in accordance with ICH Harmonized Guideline for Good Clinical Practice (ICH GCP) and local legislation prior to admission to the trial SRD part only: Evidence of diabetic macular ischemia (DMI) per investigator´s judgement, defined as any degree of disruption of retinal vascularity in superficial and/or deep retinal plexus in OCTA Best-corrected Visual activity (VA) in the non-study eye better than best-corrected VA in the study-eye, if both eyes are eligible and have identical VA the investigator may select the study eye. Best-corrected VA ≤55 letters (20/80) or worse MD part only: Presence of significant DMI: large foveal avascular zone defined as those with ≥0.5mm2 area in superficial vascular complex (SVC) present on optical coherence tomography angiography. If FAZ is <0.5mm2 then enlarged peri-foveal inter-capillary space in at least 1 quadrant will be sufficient. If both eyes are eligible, the investigator may select either eye to be the study eye. Best-corrected VA ≤ 85 letters (20/20) or worse Exclusion Criteria: SRD part only: Participants receiving intravitreal (IVT) injections for active diabetic macular edema (DME, injections: anti-vascular endothelial growth factor (VEGF), steroids) and macular laser in the study eye in the previous 3 months prior to enrolment Participants receiving anti-VEGF IVT injections for active PDR in the study eye in the previous 3 months prior to enrolment Current or planned use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol) Additional eye disease in the study eye that could compromise best corrected VA (BCVA) with visual field loss, uncontrolled glaucoma (IOP>24), age related macular degeneration, history of ischemic optic neuropathy or retinal vascular occlusion, symptomatic vitreomacular traction, or genetic disorders such as retinitis pigmentosa; history of high myopia > 8 diopters in the study eye. Anterior segment and vitreous abnormalities in the study eye that would preclude adequate observation with SD-OCT Any intraocular surgery in the study eye within 3 months prior to screening Aphakia or total absence of the posterior capsule. Yttrium aluminium garnet (YAG) laser capsulotomy in the study eye if performed less than 3 months prior to enrolment Participants not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator´s opinion, makes the patient an unreliable trial participant) Previous participation in this trial or in other trials with IVT injections administered within 3 months. Further exclusion criteria apply. MD part only: DME, defined as a central subfield thickness (CST) ≥305 micrometer (μm) for men and ≥290 μm women measured with optovue (Optical coherent tomography) OCT in the study eye Participants receiving IVT injections for active DME (anti-VEGF, steroids) and macular laser in the study eye in the previous 3 months prior to enrolment Participants receiving anti-VEGF IVT injections for active PDR in the study eye in the previous 3 months prior to enrolment Heavily lasered macula in the study eye per investigator's judgement History of vitrectomy in the study eye Epiretinal membrane with extended foveal contour distortion in the study eye per investigator's judgement Current or planned use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol) Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SRD part: BI 764524<br>SRD part: BI 764524 | Drug: BI 764524<br>* BI 764524<br>|
| Sham Comparator: MRD part: Sham control of BI 764524<br>MRD part: Sham control of BI 764524 | Drug: Sham control of BI 764524<br>* Sham control of BI 764524<br>|
| Experimental: MRD part: BI 764524<br>MRD part: BI 764524 | Drug: BI 764524<br>* BI 764524<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single rising dose (SRD) part: Number of participants with dose limiting events | Number of patients with dose limiting events (DLEs) from drug administration till day 8 (7 days after treatment). | 14 weeks | 
| Multiple dosing (MD) part: Number of patients with drug related adverse events (AEs) from drug administration till end of study (EOS) |  | 22 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SRD part: Number of patients with drug related AEs at EOS |  | 14 weeks | 
| SRD part: Number of patients with ocular AEs (eye disorders) at EOS |  | 14 weeks | 
| MD part: Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) in superficial and combined vascular complex at Visit 5 |  | 12 weeks | 
| MD part: Change from baseline of the size of the FAZ in OCTA in superficial and combined vascular complex at Visit 7 |  | 22 weeks | 
| MD part: Change from baseline of best corrected visual acuity (BCVA) at Visit 3 |  | 4 weeks | 
| MD part: Change from baseline of BCVA at Visit 4 |  | 8 weeks | 
| MD part: Change from baseline of BCVA at Visit 5 |  | 12 weeks | 
| MD part: Change from baseline of BCVA at Visit 6 |  | 16 weeks | 
| MD part: Change from baseline of BCVA at Visit 7 |  | 22 weeks | 
| MD part: Change from baseline of central retinal thickness (SD-OCT) at Visit 3 |  | 4 weeks | 
| MD part: Change from baseline of central retinal thickness (SD-OCT) at Visit 4 |  | 8 weeks | 
| MD part: Change from baseline of central retinal thickness (SD-OCT) at Visit 5 |  | 12 weeks | 
| MD part: Change from baseline of central retinal thickness (SD-OCT) at Visit 6 |  | 16 weeks | 
| MD part: Change from baseline of central retinal thickness (SD-OCT) at Visit 7 |  | 22 weeks | 
| MD part: Number of patients with ocular AEs at EOS |  | 22 weeks |