A Study to Test Different Doses of BI 836880 in Patients With an Eye Disease Called Wet Age-related Macular Degeneration (wAMD)

Study Overview
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Brief Summary
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This is a study in people with an eye disease called wet age-related macular degeneration (wAMD). The purpose of the study is to find out how well different doses of a medicine called BI 836880 are tolerated. People can participate if they are at least 55 years old and if they have new blood vessels in their eyes despite treatment (anti-VEGF therapies). The study has 2 parts. In the first part, people get only 1 dose of BI 836880. This part takes 6 weeks. In the second part, people get 3 times the same dose of BI 836880. This part takes 6 months. BI 836880 is injected into the eye. During the entire study doctors regularly check the health of the participants.

Official Title
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Safety, Tolerability and Pharmacodynamics of Single Rising Intravitreal and Multiple Rising Intravitreal Doses of BI 836880 in Patients With wAMD (Open Label, Non-randomized, Uncontrolled).

Conditions
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Wet Macular Degeneration

Intervention / Treatment
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* Drug: BI 836880


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: SRD part and MRD cohort 1 (treatment-resistant patients with wAMD): Men and women over the age of 55 with active Choroidal Neovascularisation (CNV) secondary to age-related macular degeneration (AMD) despite anti-Vascualr endothelial growth factor (VEGF) therapies (at least 3 prior injections with the last injection within 16 to 4 weeks before treatment). Active CNV secondary to AMD is to be defined either by recent fluorescein or optical coherence tomography (OCT) angiogram within 4 weeks prior to screening or fluorescein or OCT angiogram obtained prior to first anti VEGF-treatment to confirm the diagnosis and still active according to investigator judgement. For MRD part only: Central subfield retinal thickness >300 microns in the study eye on Heidelberg Spectralis Spectral Domain Optical Coherence Tomography (SD-OCT). Presence of sub- and/or intraretinal fluid on SD-OCT in the study eye. Any active CNV with subfoveal leakage in the study eye as determined by OCT No subretinal hemorrhage involving the fovea in the study eye. No significant subfoveal fibrosis or atrophy on SD-OCT in the study eye that, in the opinion of the investigator, is able to prevent improvement in best corrected visual acuity (BCVA) and/or central subfield thickness (CSFT). Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) VA in the study eye between 75 and 24 letters inclusive (approximately 20/32 and 20/320 or 6/9.5 and 6/95) at screening. Best-corrected 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. Male or female patients. Women of childbearing potential (WOCBP) cannot be included. Men able to father a child must be ready and able to use 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. Signed informed consent consistent with ICH GCP guidelines and local legislation prior to participation in the trial, which includes medication washout and restrictions. Not under any administrative or legal supervision or under institutionalization due to regulatory or juridical order. MRD cohort 2 (treatment-naive patients with wAMD): No subretinal hemorrhage involving the fovea in the study eye. No significant subfoveal fibrosis or atrophy on SD-OCT in the study eye that, in the opinion of the investigator, is able to prevent improvement in BCVA and/or CSFT. Male or female patients. Women of childbearing potential (WOCBP) cannot be included. Men able to father a child must be ready and able to use 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. Signed informed consent consistent with ICH GCP guidelines and local legislation prior to participation in the trial, which includes medication washout and restrictions. Not under any administrative or legal supervision or under institutionalization due to regulatory or juridical order. Men and women over the age of 55 with treatment-naïve CNV secondary to AMD. Any CNV with subfoveal activity in the study eye defined as evidence of sub- and/or intraretinal fluid, or subretinal hyper-reflective material, or angiographic leakage. Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) VA in the study eye between 80 and 24 letters inclusive (approximately 20/25 and 20/320 or 6/7.5 and 6/95) at screening. Best-corrected ETDRS VA in the non-study eye 50 letters inclusive (approximately 20/100 or 6/30) or better at screening. If both eyes are eligible at screening, the study eye is the eye with the worse bestcorrected VA. MRD cohort 3 (frequently treated patients): No subretinal hemorrhage involving the fovea in the study eye. No significant subfoveal fibrosis or atrophy on SD-OCT in the study eye that, in the opinion of the investigator and with the endorsement of the Sponsor, is able to prevent improvement in BCVA. Male or female patients. Women of childbearing potential (WOCBP)1 cannot be included.Men able to father a child must be ready and able to use 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. Signed informed consent consistent with ICH GCP guidelines and local legislation prior to participation in the trial, which includes medication washout and restrictions. Not under any administrative or legal supervision or under institutionalization due to regulatory or juridical order. Any CNV with subfoveal activity in the study eye defined as evidence of sub- and/or intraretinal fluid, or subretinal hyper-reflective material, or angiographic leakage. Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) VA in the study eye between 80 and 24 letters inclusive (approximately 20/25 and 20/320 or 6/7.5 and 6/95) at screening. If both eyes are eligible at screening, the study eye is the eye with the worse bestcorrected VA. Men and women over the age of 55 with diagnosed wAMD that: require frequent wAMD SoC (28-56 days between the last 3 treatments) have had ≥ 3 previous treatments with IVT SoC (ranibizumab, aflibercept, or bevacizumab) in the study eye had the last SoC injection ≥ 4 weeks, but no more than 8 weeks, before the first administration of the study drug have been on SoC treatment ≥ 6 months and are within 3 years from initial wAMD diagnosis in the study eye Exclusion criteria: Additional eye disease in the study eye that could compromise best corrected VA (BCVA) with visual field loss, uncontrolled glaucoma (intraocular pressure (IOP)> 24 mmHg on more than 2 consecutive measurements prior to screening), clinically significant diabetic maculopathy, history of ischemic optic neuropathy or retinalvascular 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 prior intraocular surgery in the study eye other then uneventful lens replacement for cataract within 3 months prior to screening. Aphakia or total absence of the posterior capsule. Yttrium aluminum garnet (YAG) laser capsulotomy permitted, more than 1 month prior to enrollment in the study eye. 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). Medical history or condition: Uncontrolled diabetes mellitus, with hemoglobin A1c (HbA1c) > 10%, myocardial infarction or stroke within 12 months of screening, active bleeding disorder, concomitant use of warfarin or anticoagulation therapy (use of antiplatelet therapy such as aspirin is allowed), major surgery within 1 month of screening or when planned within the study period, hepatic impairment, uncontrolled hypertension. Patients with a clinically relevant abnormal screening haematology, blood chemistry, or urinalysis, if the abnormality defines a significant disease as defined in other exclusion criteria. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2.0-fold the upper limit of normal at screening. Patients with total bilirubin 2.5x upper limit of normal at screening. Patient with impaired renal function defined as calculated glomerular filtration rate (GFR) < 30 mL/min. Significant alcohol or drug abuse within past 2 years per investigator judgement. Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 55 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 836880<br>Single Rising Dose part followed by a Multiple Rising Dose part | Drug: BI 836880<br>* Solution for Intravitreal (IVT) injection<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 patients with ocular dose limiting events (DLEs) from drug administration until end of trial (EOT) |  | Up to 43 days | 
| Multiple Rising Dose (MRD) part: Number of patients with drug related Adverse Events (AEs) from drug administration until end of trial (EOT) |  | Up to 169 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Rising Dose (SRD) part: Number of patients with drug related Adverse Events (AEs) |  | Up to 43 days | 
| Single Rising Dose (SRD) part: Number of patients with any ocular Adverse Events (AEs) in the study eye |  | Up to 43 days | 
| Multiple Rising Dose (MRD) part: Percent change from baseline in Central Subfield Thickness (CSFT) in the study eye at Week 12 (Visit 5), for each dose |  | Baseline, Week 12 | 
| Multiple Rising Dose (MRD) part: Change from baseline in Best Corrected Visual Acuity (BCVA) in the study eye at Week 12 (Visit 5) |  | Baseline, Week 12 | 
| Multiple Rising Dose (MRD) part: Time to recurrence after the last treatment |  | Up to 169 days | 
| Multiple Rising Dose (MRD) part: Number of patients with any ocular AEs in the study eye |  | Up to 169 days |