HORNBILL: A Study to Test Different Doses of BI 764524 in... | NCT04424290

NCT04424290

ID	Type	Description	Link
2019-004432-28	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Single-rising dose part - low dose BI 764524	Experimental	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of low dose BI 764524.	Drug: BI 764524
Single-rising dose part - medium dose BI 764524	Experimental	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of medium dose BI 764524.	Drug: BI 764524
Single-rising dose part - high dose BI 764524	Experimental	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of high dose BI 764524.	Drug: BI 764524
Multiple dosing part - Sham	Sham Comparator	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.	Drug: Sham control of BI 764524
Multiple dosing part - high dose BI 764524	Experimental

Interventions

Name	Type	Description	Arm Group Labels	Other Names
BI 764524	Drug	BI 764524	Multiple dosing part - high dose BI 764524 Single-rising dose part - high dose BI 764524 Single-rising dose part - low dose BI 764524

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Single-rising Dose (SRD) Part - The Number of Patients With Dose Limiting Events (DLEs) From Drug Administration Until Day 8	Single-rising dose (SRD) part - The number of patients with dose limiting events (DLEs) from drug administration until Day 8 (7 days after treatment).	From drug administration (day 1) till day 8, Up to 7±2 days.
Multiple Dosing (MD) Part - the Number of Patients With Drug-related Adverse Events (AEs) From Drug Administration Until End of Trial.	Multiple dosing (MD) part - the number of patients with drug-related Adverse Events (AEs) from drug administration until End of Trial.	From drug administration (day 1) till End of Trial, up to 23 weeks.

Secondary Outcomes

Measure	Description	Time Frame
SRD Part - Number of Patients With Drug-related Adverse Events at End of Trial	SRD part - Number of patients with drug-related Adverse Events at End of Trial.	From drug administration (day 1) till End of Trial, up to 15 weeks.
SRD Part - Number of Patients With Ocular Adverse Events (Eye Disorders) at End of Trial

Eligibility Module

Eligibility Criteria

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.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Trinity Research		Dothan	Alabama	36301	United States
Retina-Vitreous Associates Medical Group

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35978329	Derived	Chong V, Nguyen QD, Sepah Y, Giani A, Pearce E. 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. Trials. 2022 Aug 17;23(1):669. doi: 10.1186/s13063-022-06527-y.

Label	URL
Related Info	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Single-rising Dose Part - Low Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of low dose BI 764524.
FG001	Single-rising Dose Part - Medium Dose BI 764524

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 7, 2022	Apr 22, 2024

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Single-rising dose part - medium dose BI 764524

Treated set: all patients who were randomised and treated with at least one dose of study drug.

Arm/Group Information

ID	Title	Description
BG000	Single-rising Dose Part - Low Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of low dose BI 764524.
BG001	Single-rising Dose Part - Medium Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of medium dose BI 764524.
BG002	Single-rising Dose Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of high dose BI 764524.
BG003	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
BG004	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.
BG005	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00064.7± 15.0 BG00161.0± 7.0 BG00260.8± 6.0 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0002 BG0012 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0011 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Single-rising Dose (SRD) Part - The Number of Patients With Dose Limiting Events (DLEs) From Drug Administration Until Day 8

Single-rising dose (SRD) part - The number of patients with dose limiting events (DLEs) from drug administration until Day 8 (7 days after treatment).

Treated set: all patients who were randomised and treated with at least one dose of study drug.

Posted

Count of Participants

Participants

From drug administration (day 1) till day 8, Up to 7±2 days.

ID	Title	Description
OG000	Single-rising Dose Part - Low Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of low dose BI 764524.
OG001	Single-rising Dose Part - Medium Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of medium dose BI 764524.
OG002	Single-rising Dose Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of high dose BI 764524.

Units	Counts
Participants	OG0003 OG0013 OG0026

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020

Primary

Multiple Dosing (MD) Part - the Number of Patients With Drug-related Adverse Events (AEs) From Drug Administration Until End of Trial.

Multiple dosing (MD) part - the number of patients with drug-related Adverse Events (AEs) from drug administration until End of Trial.

Treated set: all patients who were randomised and treated with at least one dose of study drug.

Posted

Count of Participants

Participants

From drug administration (day 1) till End of Trial, up to 23 weeks.

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units	Counts
Participants

Secondary

SRD Part - Number of Patients With Drug-related Adverse Events at End of Trial

SRD part - Number of patients with drug-related Adverse Events at End of Trial.

Treated set: all patients who were randomised and treated with at least one dose of study drug.

Posted

Count of Participants

Participants

From drug administration (day 1) till End of Trial, up to 15 weeks.

ID	Title	Description
OG000	Single-rising Dose Part - Low Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of low dose BI 764524.
OG001	Single-rising Dose Part - Medium Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of medium dose BI 764524.
OG002	Single-rising Dose Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of high dose BI 764524.

Secondary

SRD Part - Number of Patients With Ocular Adverse Events (Eye Disorders) at End of Trial

SRD part - Number of patients with ocular Adverse Events (eye disorders) at End of Trial.

Treated set: all patients who were randomised and treated with at least one dose of study drug.

Posted

Count of Participants

Participants

From drug administration (day 1) till End of Trial, up to 15 weeks.

ID	Title	Description
OG000	Single-rising Dose Part - Low Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of low dose BI 764524.
OG001	Single-rising Dose Part - Medium Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of medium dose BI 764524.
OG002	Single-rising Dose Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of high dose BI 764524.

Secondary

MD Part - Number of Patients With Ocular Adverse Events (Eye Disorders) at End of Trial

MD part - Number of patients with ocular Adverse Events (eye disorders) at End of Trial.

Treated set: all patients who were randomised and treated with at least one dose of study drug.

Posted

Count of Participants

Participants

From drug administration (day 1) till End of Trial, up to 23 weeks.

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units	Counts
Participants

Secondary

MD Part - Change From Baseline of the Size of the FAZ in FTR at Visit 5

MD part - Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) in full thickness retina (FTR) at Visit 5. Results calculated as [Baseline data]-[Visit 5 data].

All patients who were randomised and treated with at least one dose of study drug and with baseline and at least 1 on-treatment post-baseline value.

Posted

Mean

Standard Deviation

Millimeter^2

Baseline (day 0) and Visit 5 (day 85±7).

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units	Counts
Participants

Secondary

MD Part - Change From Baseline of the Size of the FAZ in SVC at Visit 5

MD part - Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) in superficial vascular complex (SVC) at Visit 5. Results calculated as [Baseline data]-[Visit 5 data].

All patients who were randomised and treated with at least one dose of study drug and with baseline and at least 1 on-treatment post-baseline value.

Posted

Mean

Standard Deviation

Millimeter^2

Baseline (day 0) and Visit 5 (day 85±7).

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units	Counts
Participants

Secondary

MD Part - Change From Baseline of the Size of the FAZ in FTR at Visit 7

MD part - Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) in full thickness retina (FTR) at Visit 7. Results calculated as [Baseline data]-[Visit 7 data].

All patients who were randomised and treated with at least one dose of study drug and with baseline and at least 1 on-treatment post-baseline value.

Posted

Mean

Standard Deviation

Millimeter^2

Baseline (day 0) and Visit 7 (day 155±7).

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units	Counts
Participants

Secondary

MD Part - Change From Baseline of the Size of the FAZ in SVC at Visit 7

MD part - Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) in superficial vascular complex (SVC) at Visit 7. Results calculated as [Baseline data]-[Visit 7 data].

All patients who were randomised and treated with at least one dose of study drug and with baseline and at least 1 on-treatment post-baseline value.

Posted

Mean

Standard Deviation

Millimeter^2

Baseline (day 0) and Visit 7 (day 155±7).

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units	Counts
Participants

Secondary

MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 3

Change from baseline of best corrected visual acuity (BCVA) at Visit 3. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as [Baseline data]-[Visit 3 data].

All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.

Posted

Mean

Standard Deviation

Number of letters

Baseline (day 0) and Visit 3 (day 29±7).

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units

Secondary

MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 4

Change from baseline of best corrected visual acuity (BCVA) at Visit 4. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as [Baseline data]-[Visit 4 data].

All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.

Posted

Mean

Standard Deviation

Number of letters

Baseline (day 0) and Visit 4 (day 57±7).

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units

Secondary

MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 5

Change from baseline of best corrected visual acuity (BCVA) at Visit 5. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 5 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as [Baseline data]-[Visit 5 data].

All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.

Posted

Mean

Standard Deviation

Number of letters

Baseline (day 0) and Visit 5 (day 85±7).

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units

Secondary

MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 6

Change from baseline of best corrected visual acuity (BCVA) at Visit 6. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 6 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as [Baseline data]-[Visit 6 data].

All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.

Posted

Mean

Standard Deviation

Number of letters

Baseline (day 0) and Visit 6 (day 113±7).

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units

Secondary

MD Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 7

Change from baseline of best corrected visual acuity (BCVA) at Visit 7. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity (VA) chart starting at a test distance of 7 meter. The BCVA score was the number of letters read correctly by the patient. Results calculated as [Baseline data]-[Visit 7 data].

All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.

Posted

Mean

Standard Deviation

Number of letters

Baseline (day 0) and Visit 7 (day 155±7).

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units

Secondary

MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 3

MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 3. Results calculated as [Baseline data]-[Visit 3 data].

All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.

Posted

Mean

Standard Deviation

Micrometer

Baseline (day 0) and Visit 3 (day 29±7).

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units	Counts
Participants

Secondary

MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 4

MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 4. Results calculated as [Baseline data]-[Visit 4 data].

All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.

Posted

Mean

Standard Deviation

Micrometer

Baseline (day 0) and Visit 4 (day 57±7)

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units	Counts
Participants

Secondary

MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 5

MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 5. Results calculated as [Baseline data]-[Visit 5 data].

All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.

Posted

Mean

Standard Deviation

Micrometer

Baseline (day 0) and Visit 5 (day 85±7).

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units	Counts
Participants

Secondary

MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 6

MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 6. Results calculated as [Baseline data]-[Visit 6 data].

All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.

Posted

Mean

Standard Deviation

Micrometer

Baseline (day 0) and Visit 6 (day 113±7).

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units	Counts
Participants

Secondary

MD Part - Change From Baseline of Central Retinal Thickness (CRT) at Visit 7

MD part - Change from baseline of central retinal thickness (CRT) in Spectral domain optical coherence tomography (SD-OCT) at Visit 7. Results calculated as [Baseline data]-[Visit 7 data].

All patients who were randomised and treated with at least one dose of study drug, with data for the baseline and the corresponding visit.

Posted

Mean

Standard Deviation

Micrometer

Baseline (day 0) and Visit 7 (day 155±7).

ID	Title	Description
OG000	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.
OG001	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Single-rising Dose Part - Low Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of low dose BI 764524.	3	0	3	3	3
EG001	Single-rising Dose Part - Medium Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of medium dose BI 764524.	3	0	3	1	3
EG002	Single-rising Dose Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received one intravitreal injection of high dose BI 764524.	6	1	6	5	6
EG003	Multiple Dosing Part - Sham	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three sham intravitreal injections, each separated by 4 weeks.	10	3	10	6	10
EG004	Multiple Dosing Part - High Dose BI 764524	Pan-retinal photocoagulation (PRP)-treated proliferative diabetic retinopathy (PDR) patients with diabetic macular ischaemia (DMI) received three intravitreal injections of high dose BI 764524, each separated by 4 weeks.	21	2	21	6	21

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vitreous haemorrhage	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG0032 affected10 at risk EG0040 affected21 at risk
Injection site inflammation	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Localised infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Streptococcal sepsis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Chronic kidney disease	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Embolism	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Peripheral vascular disorder	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vertigo	Ear and labyrinth disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG0030 affected10 at risk EG0040 affected21 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Episcleritis	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Iris neovascularisation	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Ocular hyperaemia	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Photopsia	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Vitreal cells	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Vitreous detachment	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0022 affected6 at risk EG003
Vitreous floaters	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Oedema peripheral	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
COVID-19	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Blood folate increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood glucose decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Blood urea increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Intraocular pressure increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Lipase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Dizziness	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected3 at risk EG0020 affected6 at risk EG003
Facial paralysis	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Nerve compression	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected3 at risk EG0020 affected6 at risk EG003
Hypertension	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected3 at risk EG0021 affected6 at risk EG003

ID	Term
D003930	Diabetic Retinopathy

Ancestor Terms

ID	Term
D012164	Retinal Diseases
D005128	Eye Diseases
D003925	Diabetic Angiopathies
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D048909	Diabetes Complications
D003920	Diabetes Mellitus
D004700	Endocrine System Diseases

Units	Counts
Participants	OG0003 OG0013 OG0026

EG0041 affected21 at risk

EG0040 affected21 at risk

EG0041 affected21 at risk

EG0040 affected21 at risk

EG0041 affected21 at risk

EG0040 affected21 at risk

EG0042 affected21 at risk

EG0040 affected21 at risk

EG0042 affected21 at risk

EG0040 affected21 at risk

EG0042 affected21 at risk

EG0040 affected21 at risk

EG0042 affected21 at risk

EG0040 affected21 at risk

EG0041 affected21 at risk