A Study That Tests BI 1467335 in Patients With Diabetic Eye Disease (Diabetic Retinopathy). It Looks at the Way BI 1467335 is Taken up, the Effects it Has, and How Well it is Tolerated.
Condition: Diabetic Retinopathy
MeSH terms: Retinal Diseases; Diabetic Retinopathy
Intervention: BI 1467335; Placebo
Intervention description: Once daily; Once daily
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 79.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The main objective is to evaluate ocular and systemic safety and tolerability of BI 1467335
      as well as whether BI 1467335 monotherapy has a potential to improve retinal lesions in
      patients with moderately severe Non-proliferative diabetic retinopathy (NPDR) (DRSS level 47)
      or severe Non-proliferative diabetic retinopathy (NPDR) (DRSS level 53), without
      Center-involved diabetic macular edema (CI-DME)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Of legal age (according to local legislation, usually ≥ 18 years) at screening

          -  Male or female patients. Women of childbearing potential (WOCBP) 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. A list of contraception
             methods meeting these criteria is provided in the patient information.

          -  Diagnosis of diabetes mellitus (type 1 or type 2):

             --Documented diabetes by American Diabetes Association (ADA) and/or World Health
             Organization criteria

          -  Glycosylated hemoglobin (HbA1c) ≤ 12% at screening

          -  Non-proliferative diabetic retinopathy (NPDR) without center-involved diabetic macular
             edema (CI-DME) in the study eye at screening with NPDR level 47 or level 53, as
             determined by the Central reading center (CRC) by using the DR severity scale (DRSS)

          -  Best corrected visual acuity ETDRS letter score ≥ 70 letters in the study eye at
             screening

          -  Media clarity, pupillary dilation and individual cooperation sufficient for adequate
             retinal examination including fundus photographs and Optical Coherence Tomography
             (OCT)

          -  Signed and dated written informed consent in accordance with ICH-GCP and local
             legislation prior to admission to the trial

        Exclusion Criteria:

          -  Cataract surgery performed within 6 months prior to screening or planned during the
             trial in the study eye; or any additional eye disease in the study eye that, in the
             opinion of the investigator,could compromise or alter visual acuity during the course
             of the study (e.g. vein occlusion, uncontrolled intraocular pressure (IOP) >24 mmHg on
             optimal medical treatment, glaucoma with visual field loss, uveitis or other ocular
             inflammatory disease,vitreomacular traction, monocular vision, history of ischemic
             optic neuropathy, or genetic disorders such as retinitis pigmentosa)

          -  Active center-involved DME (CI-DME) on clinical examination and Optical Coherence
             Tomography (OCT) central subfield thickness in the study eye above 300 μm as measured
             by Optovue OCT or above 320 μm as measured by Heidelberg OCT

          -  Anterior segment and vitreous abnormalities in the study eye that would compromise the
             adequate assessment of the best corrected visual acuity or an adequate examination of
             the posterior pole

          -  Evidence of neovascularization on clinical examination including active
             neovascularization of the iris (small iris tufts are not an exclusion) or angle
             neovascularization in the study eye, ruled out by gonioscopy (documented in the last 4
             weeks before screening or performed at screening)

          -  Prior pan-retinal photocoagulation (defined as ≥ 100 burns placed previously outside
             of the posterior pole) in the study eye

          -  Treatment of either DME or DR with macular laser within 3 months prior to screening,
             or intraocular injections of medication within 6 months prior to screening, and no
             more than 4 prior intraocular injections in the study eye at any time in the past

          -  Patients treated with Monoamine Oxidase (MAO) inhibitors or drugs that may have
             potential side effects due to MAO inhibition

          -  Current or planned, during the trial, use of medications known to be toxic to the
             retina, lens or optic nerve, or cause vision loss

          -  Patients who must or wish to continue the intake of other restricted medications or
             any drug considered likely to interfere with the safe conduct of the trial

          -  Estimated Glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 calculated by Chronic
             Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at screening, or where
             the investigator expects filtration rate is likely to drop below 60 mL/min/1.73m2
             during the trial

          -  Alanine transaminase (ALT) or aspartate transaminase (AST) greater than 2.0-fold the
             upper limit of normal, or total bilirubin > 1.5x upper limit of normal.

          -  Uncontrolled arterial hypertension defined as a single measurement of systolic blood
             pressure >180 mmHg, or two consecutive measurements of systolic blood pressure > 160
             mmHg and/or diastolic blood pressure >100 mmHg on optimal medical regimen at
             screening. If blood pressure is brought to ≤ 160/100 mmHg by antihypertensive
             treatment until randomization, individual can become eligible.

          -  Wolff-Parkinson-White Syndrome, baseline QTc > 450 ms (Fridericia's formula), family
             history of long QT, or on medication prolonging QT time at screening or planned
             initiation during the trial

          -  Diagnosis of a serious or unstable systemic or eye disease and other conditions that,
             in the clinical judgment of the investigator, are likely to interfere with the
             analyses of safety and efficacy in this study. Patients with an expected life
             expectancy of less than 2 years are also excluded.

          -  Active known or suspected chronic or relevant acute infections, such as HIV (Human
             Immunodeficiency Virus)\viral hepatitis, or tuberculosis. QuantiFERON® TB test and HBs
             Ag test will be performed during screening. Patients with a positive test result may
             participate in the study if further work up (according to local practice/guidelines)
             establishes conclusively that the patient has no evidence of active infection.

          -  Any documented active or suspected malignancy or history of malignancy within 5 years
             prior to screening, except appropriately treated basal cell carcinoma of the skin or
             in situ carcinoma of uterine cervix.

          -  Chronic alcohol or drug abuse or any condition that, in the investigator's opinion,
             makes them an unreliable study participant or unlikely to complete the trial

          -  Known hypersensitivity to any component of the trial drug and/or allergy to
             fluorescein dye

          -  Major surgery (major according to the investigator's assessment) performed within 12
             weeks prior to randomization or planned during the trial, e.g. hip replacement

          -  Currently enrolled in another investigational drug trial, or less than 30 days or 5
             times half-life of the investigational drug, whichever is longer, since ending another
             investigational drug trial from the screening visit in this trial or receiving other
             investigational treatment(s); patients participating in a purely observational trial
             will not be excluded.

          -  Previous randomization in this trial

          -  Women who are pregnant, nursing, or who plan to become pregnant while in the trial

          -  Any other clinical condition that, in the opinion of the investigator, would
             jeopardize patient safety while participating in this clinical trial.