A Study to Test Whether BI 764524 Helps People With an Eye Condition Called Diabetic Retinopathy

Boehringer Ingelheim

Status and phase: Enrolling; Phase 2

Conditions: Diabetic Retinopathy

Treatments: Drug: BI 764524; Drug: Aflibercept (Eylea®) - US only; Drug: Sham comparator to BI 764524

Study type: Interventional

Funder types: Industry

Identifiers

NCT06321302

2023-508891-12-00 (Registry Identifier)

U1111-1299-0915 (Registry Identifier)

1436-0007

Details and patient eligibility

About

This study is open to adults with diabetic retinopathy. People who have non-proliferative diabetic retinopathy of moderate or high severity can join the study.

The purpose of this study is to find out whether a medicine called BI 764524 helps people with diabetic retinopathy. The study also aims to find a suitable treatment plan for BI 764524. Participants are put into 5 groups by chance. Participants in groups 1, 2, and 3 get BI 764524. Over 1 year, they get a different number of injections of the same dose of BI 764524 injected into 1 eye. During some visits, participants may get a sham control, which is done like an eye injection but without a needle, so that participants will not know how many injections of BI 764524 they received. Participants in group 4 only get a sham control. Participants in group 5 (only in the USA) get aflibercept or sham injections during some visits. Aflibercept is a medicine already used to treat diabetic retinopathy.

Participants are in the study for one and a half years. During this time, they visit the study site at least 16 times. During this time, doctors regularly do eye exams and visual tests to assess the severity of participants' eye condition. After 1 year of treatment, researchers look at the number of participants with eye improvements. To do so, they compare eye damage and certain severe eye problems between the groups of participants. The doctors also regularly check participants' health and take note of any unwanted effects.

Enrollment: 178 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

General inclusion criteria

• Diagnosis of diabetes mellitus (DM) under regular treatment with Haemoglobin A1c (HbA1c) (glycated haemoglobin) (HbA1c) <12%; DM should be under regular investigation by a trained specialist as per local standard of care prior to and during the trial
• Age ≥18 years at time of signing Informed Consent Form (ICF)

Ocular inclusion criteria: study eye

• Moderately severe to severe non-proliferative diabetic retinopathy (NPDR) (Diabetic Retinopathy Severity Scale (DRSS) 47 to 53) based on early treatment diabetic retinopathy study (ETDRS) 7-field grading as confirmed by the central reading centre (CRC) at screening
• Ultra-widefield fluorescein angiography (UWF-FA) image gradable for presence of retinal non-perfusion (RNP) as confirmed by the CRC at screening
• Visual acuity: best corrected visual acuity (BCVA) letter score of ≥49 letters (approximate Snellen equivalent of 20/100 or better) using ETDRS chart at starting distance of 4 meter (m) at screening
• Sufficiently clear ocular media, adequate pupillary dilation, and fixation to permit quality fundus imaging

Main exclusion criteria in study eye:

- Evidence of active retinal neovascularisation (NV) on clinical exam and/or ultra-widefield colour fundus photography (UWF-CFP) within the ETDRS 7-field, confirmed by the CRC grading

The following are permitted if, based on the assessment of the investigator, do not require acute treatment:

• Small neovascular lesions within the ETDRS 7-field that are detected only on UWF-FA, but not on clinical exam or colour fundus photography (CFP)

• Neovascularisations outside of the ETDRS 7-field on ultra-widefield imaging

  • Evidence of active NV of the iris (small iris tufts are not an exclusion) or in the anterior chamber angle
  • Prior pan-retinal photocoagulation (PRP). Peripheral scatter or targeted laser treatment in up to 1 quadrant outside the ETDRS 7-field area is permitted if it was performed at least 6 months prior to Day 1
  • CI-DME, defined as central subfield thickness (CST) ≥320 micrometer (μm) as measured by Heidelberg Spectralis optical coherence tomography (OCT) and confirmed by central reading centre (CRC) at screening (equivalent measurements from other OCT machines may be accepted); participants with a CST of 320-330 μm can be included if, in the opinion of the investigator, the participant is not expected to require treatment for CI-DME during the duration of the study (e.g. no profound impact on BCVA, stable CST, etc.)
  • Previous treatment in the study eye for NPDR and/or diabetic macular edema (DME) with intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) (including anti-VEGF/Ang2) or short acting corticosteroid drugs (e.g. triamcinolone) within 6 months prior to Day 1 or dexamethasone intravitreal drug delivery system (Ozurdex) within 12 months prior to Day 1 (referred to elsewhere as 'previous IVT treatment').
  • Any previous IVT treatment other than anti-VEGF, and steroids. Previous fluocinolone acetonide intravitreal implant (Iluvien) is not allowed
  • Refractive error of more than -8 dioptres of myopia (spherical equivalent) in the study eye. For patients having undergone refractive or cataract surgery in the study eye, either the pre-operative refractive error or the axial length measurement should be used, at the investigator's discretion. Axial length should be less than 26 mm
  • Any concurrent or past ocular condition in the study eye which, in the judgement of the investigator, could:

• Require medical or surgical intervention during the study period to prevent or treat vision loss (e.g. advanced cataract, history of retinal detachment or macular hole (Stage 3 or 4) in the study eye)

• Could likely contribute to a significant loss of BCVA during the study period if left untreated (e.g. advanced epiretinal membrane and/or vitreomacular traction, active or history of optic neuritis in either eye)

• Contraindicate the use of the investigational drug, or may render the patient at high risk for treatment complications (e.g. active infectious or non-infectious conjunctivitis/keratitis in either eye; history of recurrent infectious or inflammatory ocular disease in either eye (e.g. uveitis)

• May affect interpretation of the study results (e.g. central atrophy of the retinal pigment epithelium or photoreceptors; age-related macular degeneration, hereditary retinal degenerative diseases, myopic macular degeneration, past, current or planned use of medications known to be toxic to the retina, lens or optic nerve (e.g. deferoxamine, chloroquine/hydroxychloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol); history of central serous chorioretinopathy, ischemic optic neuropathy or retinal vascular occlusion

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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178 participants in 3 patient groups

BI 764524

Experimental group

Description:

BI 764524

Treatment:

Drug: BI 764524

Sham comparator to BI 764524

Sham Comparator group

Description:

Sham comparator to BI 764524

Treatment:

Drug: Sham comparator to BI 764524

Aflibercept (Eylea®) - US only

Active Comparator group

Description:

Aflibercept (Eylea®) - US only

Treatment:

Drug: Aflibercept (Eylea®) - US only