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

Phase 1

Completed

Conditions: Diabetic Retinopathy

Interventions: Drug: BI 765128
Other: Sham comparator

Registration Number: NCT04919499

Lead Sponsor: Boehringer Ingelheim

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 46

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Single rising dose part: low-dose BI 765128	BI 765128	Diabetic retinopathy (DR) patients with Diabetic Macular Ischemia (DMI) previously treated with panretinal photocoagulation (PRP) received one single intravitreal injection of low-dose BI 765128.
Single rising dose part: medium-dose BI 765128	BI 765128	Diabetic retinopathy (DR) patients with Diabetic Macular Ischemia (DMI) previously treated with panretinal photocoagulation (PRP) received one single intravitreal injection of medium-dose BI 765128.
Single rising dose part: high-dose BI 765128	BI 765128	Diabetic retinopathy (DR) patients with Diabetic Macular Ischemia (DMI) previously treated with panretinal photocoagulation (PRP) received one single intravitreal injection of high-dose BI 765128.
Multiple dose part: high-dose BI 765128	BI 765128	Diabetic retinopathy (DR) patients with Diabetic Macular Ischemia (DMI) previously treated with panretinal photocoagulation (PRP) received 3 single intravitreal injection of high-dose BI 765128 at week 1, 4 and 8.
Multiple dose part: Sham	Sham comparator	Diabetic retinopathy (DR) patients with Diabetic Macular Ischemia (DMI) previously treated with panretinal photocoagulation (PRP) received 3 single intravitreal sham injection at week 1, 4 and 8.

Primary Outcome Measures

Name	Time	Method
Single Rising Dose Part - Number of Subjects With Ocular Dose Limiting Events (DLEs) From Drug Administration Until Day 8 (7 Days After Treatment)	From initial drug administration (day 1) until day 8.	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.
Multiple Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) From Drug Administration Until End of Study (EOS)	From first drug administration to end of the multiple dose part of the study, i.e., up to day 141±7.	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.

Secondary Outcome Measures

Name	Time	Method
Single Rising Dose Part - Number of Subjects With Drug Related Adverse Events (AEs) at End of Study (EOS)	From first drug administration to end of the single rising dose part of the study, i.e., up to day 99±7.	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.
Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 7	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.	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.
Single Rising Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) at End of Study (EOS)	From first drug administration to end of the single rising dose part of the study, i.e., up to day 99±7.	Number of subjects with any ocular adverse events at the end of the single rising dose part of the study.
Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 5	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.	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.
Multiple Dose Part - Change From Baseline of the Size of the Foveal Avascular Zone (FAZ) in Optical Coherence Tomography Angiography (OCTA) at Visit 6	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.	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.
Multiple Dose Part - Change From Baseline of Best Corrected Visual Acuity (BCVA) at Visit 7	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.	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.
Multiple Dose Part - Number of Subjects With Any Ocular Adverse Events (AEs) (Eye Disorders) From Drug Administration Until End of Study (EOS)	From first drug administration to end of the multiple dose part of the study, i.e., up to day 141±7.	Number of subjects with any ocular adverse events at the end of the multiple dose part of the study.

Trial Locations

Locations (24): Mid Atlantic Retina
🇺🇸
Philadelphia, Pennsylvania, United States
Central Middlesex Hospital
🇬🇧
London, United Kingdom
Bay Area Retina Associates - Walnut Creek
🇺🇸
Walnut Creek, California, United States
Moorfields Eye Hospital
🇬🇧
London, United Kingdom
Hospital Clínico San Carlos
🇪🇸
Madrid, Spain
Adelaide Eye and Retina Centre
🇦🇺
Adelaide, South Australia, Australia
California Retina Consultants
🇺🇸
Bakersfield, California, United States
Hospital Vall d'Hebron
🇪🇸
Barcelona, Spain
Hospital Miguel Servet
🇪🇸
Zaragoza, Spain
Erie Retina Research, LLC
🇺🇸
Erie, Pennsylvania, United States
Leids Universitair Medisch Centrum (LUMC)
🇳🇱
Leiden, Netherlands
Bristol Eye Hospital
🇬🇧
Bristol, United Kingdom
Oxford Eye Hospital
🇬🇧
Oxford, United Kingdom
Meridian Clinical Research, LLC
🇺🇸
Cincinnati, Ohio, United States
Riga East University Hospital
🇱🇻
Riga, Latvia
Hobart Eye Surgeons
🇦🇺
Hobart, Tasmania, Australia
Sunderland Eye Infirmary
🇬🇧
Sunderland, United Kingdom
Retina Consultants of Texas
🇺🇸
The Woodlands, Texas, United States
Austin Research Center for Retina, PLLC
🇺🇸
Austin, Texas, United States
Austin Clinical Research, LLC
🇺🇸
Austin, Texas, United States
Cumberland Valley Retina Consultants, PC.
🇺🇸
Hagerstown, Maryland, United States
Hospital Dos de Maig
🇪🇸
Barcelona, Spain
Retinal Consultants Medical Group
🇺🇸
Sacramento, California, United States
Royal Liverpool University Hospital
🇬🇧
Liverpool, United Kingdom