A Study of BI 765128 in Patients With an Eye Condition Called Diabetic Macular Ischemia Who Have Received Laser Treatment

Study Overview
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Brief Summary
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This study is open to adults with diabetic macular ischemia who have received laser treatment. The main purpose of this study is to find out whether people with diabetic macular ischemia can tolerate a medicine called BI 765128. In this study, BI 765128 is given to people for the first time. The study has 2 parts. Part A tests 3 doses of BI 765128. Participants get either a low, medium or high dose of BI 765128 as a single injection into the eye. If participants tolerate it well, the highest dose will be used in part B. In part B, participants are put into 2 groups randomly, which means by chance. 1 group gets BI 765128 as injection into the eye. The other group gets sham injections. 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. In this part, participants receive study treatment once every month for 3 months. Participants in part A are in the study for about 4 months and visit the study site about 8 times. Participants in part B are in the study for about 5 months and visit the study site about 7 times. The doctors regularly check participants' health and take note of any unwanted effects.

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 Doses (Double-masked, RandomIzed, Sham-controlleD) of BI 765128 in Panretinal photocoaGulation (PRP) Treated Diabetic rEtinopathy (DR) Patients With Diabetic Macular Ischemia (DMI) - the PARTRIDGE Study

Conditions
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Diabetic Retinopathy

Intervention / Treatment
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* Drug: BI 765128
* Other: Sham comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part A Panretinal photocoagulation-treated diabetic retinopathy (DR) patients with either no or inactive retinal neovascularization per investigator judgement in the study eye Male or female subjects of age ≥ 18 years Evidence of diabetic macular ischemia (DMI) per investigator´s judgement, defined as any degree of disruption of retinal vascularity in optical coherent tomography angiography (OCTA) Glycosylated Hemoglobin, Type A1C (HbA1c) of ≤ 12.0% Best-corrected visual acuity (VA) ≤75 letters (20/32) in the study eye Best corrected visual acuity (VA) in the non-study eye must be equal to or better than best corrected VA in the study eye. If both eyes are eligible and have identical best corrected VA the investigator may select the study eye. 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 method 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. Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial Part B: Panretinal photocoagulation-treated diabetic retinopathy (DR) patients with either no or inactive retinal neovascularization per investigator judgement Male or female subjects of age ≥ 18 years Presence of significant diabetic macular ischemia (DMI): Large foveal avascular zone (FAZ) defined as those with ≥0.5mm2 area present on optical coherent tomography angiography (OCTA). If FAZ is <0.5mm2 then an enlarged peri-foveal inter-capillary space in at least 1 quadrant will be sufficient. Glycosylated Hemoglobin, Type A1C (HbA1c) of ≤ 12.0% Best-corrected visual acuity (VA) ≤85 letters (20/20) in the study eye If both eyes are eligible, the investigator may select either eye to be the study eye. 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 method 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. Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial Exclusion Criteria: Part A: Subjects receiving intravitreal (IVT) injections for active Diabetic Macular Edema (DME) (anti-vascular endothelial growth factor (VEGF), steroids) and macular laser in the previous 3 months to screening in the study eye Subjects receiving anti-VEGF IVT injections for active diabetic retinopathy (DR) in the previous 3 months to screening in the study eye Current or planned use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoxamine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol) Additional progressive eye disease in the study eye that could compromise best corrected visual acuity (VA) (best corrected visual acuity (BCVA)), uncontrolled glaucoma (intra-ocular pressure (IOP)>24), 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 spectral domain optical coherence tomography (SD-OCT) and optical coherent tomography angiography (OCTA). Any intraocular surgery in the study eye within 3 months prior to screening Glaucoma tube shunts Aphakia or total absence of the posterior capsule. Yttrium aluminum garnet (YAG) laser capsulotomy permitted, if completed more than 3 months prior to screening, in the study eye Subjects 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 subject an unreliable trial subject) Further exclusion criteria apply Part B: Diabetic Macular Edema (DME), defined as a Central Subfield Thickness (CST) ≥ 305μm for men and ≥ 290 μm for women (Optovue Angiovue) in the study eye Subjects receiving intravitreal (IVT) injections for active DME (anti-vascular endothelial growth factor (VEGF), steroids) and macular laser in the previous 3 months to screening in the study eye Subjects receiving anti-VEGF intravitreal IVT injections for active Diabetic Retinopathy (DR) in the previous 3 months to screening in the study eye Heavily lasered macula in the study eye per investigator judgement History of vitrectomy in the study eye Epiretinal membrane with extended foveal contour distortion in the study eye Current or planned use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoxamine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol) Additional eye disease in the study eye that could compromise best corrected VA (BCVA). Significant visual field loss, uncontrolled glaucoma (IOP>24), clinically significant diabetic maculopathy, 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 and OCTA 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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: BI 765128 low dose<br> | Drug: BI 765128<br>* BI 765128<br>|
| Experimental: Part A: BI 765128 medium dose<br> | Drug: BI 765128<br>* BI 765128<br>|
| Experimental: Part A: BI 765128 high dose<br> | Drug: BI 765128<br>* BI 765128<br>|
| Experimental: Part B: BI 765128<br>Highest safe dose from Part A | Drug: BI 765128<br>* BI 765128<br>|
| Sham Comparator: Part B: Sham comparator<br> | Other: Sham comparator<br>* Sham comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Number of subjects with ocular dose limiting events (DLEs) from drug administration until day 8 (7 days after treatment) |  | up to 7 days | 
| Part B: Number of subjects with drug related Adverse Events (AEs) from drug administration until end of study (EOS) |  | up to 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Number of subjects with drug related Adverse Events (AEs) at end of study (EOS) |  | up to 14 weeks | 
| Part A: Number of subjects with any ocular Adverse Events (AEs) (eye disorders) at end of study (EOS) |  | up to 14 weeks | 
| Part B: Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) at visit 5 |  | up to 12 weeks | 
| Part B: Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) at visit 6 |  | up to 16 weeks | 
| Part B: Change from baseline of the size of the foveal avascular zone (FAZ) in optical coherence tomography angiography (OCTA) at visit 7 |  | up to 20 weeks | 
| Part B: Change from baseline of best corrected visual acuity (BCVA) at Visit 7 |  | up to 20 weeks | 
| Part B: Number of subjects with any ocular Adverse Events (AEs) (eye disorders) from drug administration until end of study (EOS) |  | up to 20 weeks |