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

NCT04919499 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 1451-00012020-005425-87
• Study Type: interventional
• Target: 46
• Locations: 6 countries
• Sites: 25

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.

Conditions

Diabetic Retinopathy

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

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

Secondary Outcomes (7)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (5)

Single rising dose part: low-dose BI 765128

EXPERIMENTAL

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.

Drug: BI 765128

Single rising dose part: medium-dose BI 765128

EXPERIMENTAL

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.

Drug: BI 765128

Single rising dose part: high-dose BI 765128

EXPERIMENTAL

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.

Drug: BI 765128

Multiple dose part: high-dose BI 765128

EXPERIMENTAL

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.

Drug: BI 765128

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.

Other: Sham comparator

Interventions

BI 765128 DRUG

BI 765128

Multiple dose part: high-dose BI 765128; Single rising dose part: high-dose BI 765128; Single rising dose part: low-dose BI 765128; Single rising dose part: medium-dose BI 765128

Sham comparator OTHER

Sham comparator

Multiple dose part: Sham

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (25)

California Retina Consultants

Bakersfield, California, 93309, United States

Location

Retinal Consultants Medical Group

Sacramento, California, 95825, United States

Location

Bay Area Retina Associates - Walnut Creek

Walnut Creek, California, 94598, United States

Location

Cumberland Valley Retina Consultants, PC.

Hagerstown, Maryland, 21740, United States

Location

Meridian Clinical Research, LLC

Cincinnati, Ohio, 45219, United States

Location

Erie Retina Research, LLC

Erie, Pennsylvania, 16507, United States

Location

Mid Atlantic Retina

Philadelphia, Pennsylvania, 19107, United States

Location

Austin Research Center for Retina, PLLC

Austin, Texas, 78705, United States

Location

Austin Clinical Research, LLC

Austin, Texas, 78750, United States

Location

Retina Consultants of Texas

Bellaire, Texas, 77401, United States

Location

Retina Consultants of Texas

The Woodlands, Texas, 77384, United States

Location

Adelaide Eye and Retina Centre

Adelaide, South Australia, 5000, Australia

Location

Hobart Eye Surgeons

Hobart, Tasmania, 7008, Australia

Location

Riga East University Hospital

Riga, 1006, Latvia

Location

Leids Universitair Medisch Centrum (LUMC)

Leiden, 2333 ZA, Netherlands

Location

Hospital Dos de Maig

Barcelona, 08025, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Miguel Servet

Zaragoza, 50009, Spain

Location

Bristol Eye Hospital

Bristol, BS1 2LX, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

Moorfields Eye Hospital

London, EC1V 2PD, United Kingdom

Location

Central Middlesex Hospital

London, NW10 7NS, United Kingdom

Location

Oxford Eye Hospital

Oxford, OX3 9DU, United Kingdom

Location

Sunderland Eye Infirmary

Sunderland, SR2 9HP, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Diabetic Retinopathy

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Description to masking: In Part A no masking will be performed. In Part B participant and investigator will be masked. Description to randomisation: In Part A no randomisation will be performed. In Part B randomisation will be performed.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: June 9, 2021
• Study Start: July 30, 2021
• Primary Completion: August 7, 2023
• Study Completion: August 7, 2023
• Last Updated: November 21, 2024
• Results First Posted: August 27, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

LA (1); AU (2); NL (1); US (11); ES (4); GB (6)