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

Phase 2CompletedNCT04919499

Boehringer Ingelheim46 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Diabetic Retinopathy

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (25)

California Retina Consultants

Bakersfield, California, United States

Retinal Consultants Medical Group

Sacramento, California, United States

Bay Area Retina Associates - Walnut Creek

Walnut Creek, California, United States

Cumberland Valley Retina Consultants, PC.

Hagerstown, Maryland, United States

Meridian Clinical Research, LLC

Cincinnati, Ohio, United States

Erie Retina Research, LLC

Erie, Pennsylvania, United States

Mid Atlantic Retina

Philadelphia, Pennsylvania, United States

Austin Research Center for Retina, PLLC

Austin, Texas, United States

Austin Clinical Research, LLC

Austin, Texas, United States

Retina Consultants of Texas

Bellaire, Texas, United States

...and 15 more locations

Outcomes

Primary Outcomes

Single Rising Dose Part - Number of Subjects With Ocular Dose Limiting Events (DLEs) From Drug Administration Until Day 8 (7 Days After Treatment)

Dose limiting events were defined in the clinical trial protocol as any of the following occurrences in the eye being studied during the evaluation period: * development of sterile endophthalmitis and/or sterile inflammation of the vitreous of 3+ (out of 0, 0.5+,1+,2+,3+ and 4+, where 0 is clear vitreous and 4+ is an obscured vitreous) according to the NEI (National Eye Institute) Grading of vitreous haze, and anterior chamber cells of 3+ (out of 0, 0.5+,1+,2+,3+ and 4+, where 0 is no inflammation and 4+ is severe inflammation) according to the Standardization of Uveitis Nomenclature (SUN) working group (WG) grading scheme for 5 or more days; * visual loss of more than 15 letters at any given time-point; persistent intra-ocular pressure over 30 mmHg for 3 days; * and signs of vascular occlusion in a first (the main branch) or second degree (the vessel after the first bifurcation of the main branch) retinal vessel.

Time frame: From initial drug administration (day 1) until day 8.

Multiple Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) From Drug Administration Until End of Study (EOS)

Number of subjects with adverse events assessed as drug related by the investigator from first drug administration to end of the multiple dose part of the study.

Time frame: From first drug administration to end of the multiple dose part of the study, i.e., up to day 141±7.

Secondary Outcomes

Single Rising Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) at End of Study (EOS)

Number of subjects with adverse events assessed as drug related by the investigator from first drug administration to end of the single rising dose part of the study.

Time frame: From first drug administration to end of the single rising dose part of the study, i.e., up to day 99±7.

Single Rising Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) at End of Study (EOS)

Number of subjects with any ocular adverse events at the end of the single rising dose part of the study.

Time frame: From first drug administration to end of the single rising dose part of the study, i.e., up to day 99±7.

Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 5

This outcome measured the change in size of the foveal avascular zone (FAZ) from baseline to visit 5 of the multiple dose part of the trial by optical coherence tomography angiography (OCTA). Results were calculated as \[Visit 5\] -\[Baseline\]. A mixed model with repeated measurements (MMRM) was used for the analysis with fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors.

Time frame: MMRM included measurements at baseline, day 29±3, day 57±3, day 85±7, day 113±7 and day 141±7. Change from baseline values at day 85±7 (visit 5) is reported.

Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 6

This outcome measured the change in size of the foveal avascular zone (FAZ) from baseline to visit 6 of the multiple dose part of the trial by optical coherence tomography angiography (OCTA). Results were calculated as \[Visit 6\] - \[Baseline\]. A mixed model with repeated measurements (MMRM) was used for the analysis with fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors.

Time frame: MMRM included measurements at baseline, day 29±3, day 57±3, day 85±7, day 113±7 and day 141±7. Change from baseline values at day 113±7 (visit 6) is reported.

Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 7

This outcome measured the change in size of the foveal avascular zone (FAZ) from baseline to visit 7 of the multiple dose part of the trial by optical coherence tomography angiography (OCTA). Results were calculated as \[Visit 7\] - \[Baseline\]. A mixed model with repeated measurements (MMRM) was used for the analysis with fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors.

Time frame: MMRM included measurements at baseline, day 29±3, day 57±3, day 85±7, day 113±7 and day 141±7. Change from baseline values at day 141±7 (visit 7) is reported.

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

This outcome measured the absolute change in best corrected visual acuity (BCVA) from baseline to visit 7 of the multiple dose part of the trial. The BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) visual acuity chart. The BCVA score was the number of letters read correctly by the patient. Results were calculated as \[Visit 7\] - \[Baseline\] and were rounded to one decimal place. A mixed model with repeated measurements (MMRM) was used for the analysis with fixed, categorical effects of treatment at each visit and the fixed continuous effects of baseline at each visit. Visit was treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors.

Time frame: MMRM included measurements at baseline, day 29±3, day 57±3, day 85±7, day 113±7 and day 141±7. Change from baseline values at day 141±7 (visit 7) is reported.

Multiple Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) From Drug Administration Until End of Study (EOS)

Number of subjects with any ocular adverse events at the end of the multiple dose part of the study.

Time frame: From first drug administration to end of the multiple dose part of the study, i.e., up to day 141±7.