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.

Diabetic Retinopathy Clinical Trial

— ROBIN  

Official title:

A Randomized, Double-masked, Placebo-controlled Exploratory Study to Evaluate Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Orally Administered BI 1467335 for 12 Weeks With a 12 Week Follow up Period in Patients With Non-proliferative Diabetic Retinopathy Without Center-involved Diabetic Macular Edema (ROBIN Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03238963
• Other study ID #: 1386-0012
• Secondary ID: 2016-002971-9113
• Status: Completed
• Phase: Phase 2
• Start date: September 19, 2017
• Est. completion date: May 14, 2020

Study information

• Verified date: March 2021
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: May 14, 2020
• Est. primary completion date: May 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Retinal Diseases

Intervention

Drug:
• BI 1467335
Once daily
• Placebo
Once daily

Locations

Country	Name	City	State
Austria	LKH-Univ. Hospital Graz	Graz
Greece	Interbalkan Medical Center of Thessaloniki	Thessaloniki
Italy	Fondazione Centro San Raffaele del Monte Tabor	Milano
Italy	IRCCS Fondazione Bietti	Roma
Norway	Oslo Universitetssykehus HF, Ullevål sykehus	Oslo
Portugal	CHUC - Centro Hospitalar e Universitário de Coimbra, EPE	Coimbra
Portugal	Espaço Médico de Coimbra	Coimbra
Portugal	CHULC, EPE - Hospital Sto. António Capuchos	Lisboa
Spain	Hospital Dos de Maig	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Miguel Servet	Zaragoza
United Kingdom	Bradford Royal Infirmary	Bradford
United Kingdom	Bristol Eye Hospital	Bristol
United Kingdom	Frimley Park Hospital	Frimley
United Kingdom	Moorfields Eye Hospital	London
United Kingdom	Royal Victoria Infirmary	Newcastle upon Tyne
United Kingdom	Hospital of St Cross	Rugby
United Kingdom	Sunderland Eye Infirmary	Sunderland
United States	Retina Research Institute of Texas	Abilene	Texas
United States	Retina Research Center, PLLC	Austin	Texas
United States	Retina-Vitreous Associates Medical Group	Beverly Hills	California
United States	Charlotte Eye Ear Nose and Throat Associates, PA	Charlotte	North Carolina
United States	Northwestern Medical Group	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Trinity Research	Dothan	Alabama
United States	Cumberland Valley Retina Consultants, PC.	Hagerstown	Maryland
United States	Retina Consultants of Houston, PA	Houston	Texas
United States	Raj K. Maturi, MD PC	Indianapolis	Indiana
United States	New York Eye and Ear Infirmary of Mount Sinai	New York	New York
United States	Florida Retina Institute	Orlando	Florida
United States	Stanford University Medical Center	Palo Alto	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Retinal Research Institute, LLC	Phoenix	Arizona
United States	NJRetina	Teaneck	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Austria,  Greece,  Italy,  Norway,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Any Ocular Adverse Events Over the On-treatment Period	Percentage of participants with any ocular adverse events over the on-treatment period was reported.	On-treatment period: from first dose of study drug until end of follow-up period, up to 24 weeks.
Secondary	Percentage of Participants With at Least 2 Steps Improvement From Baseline in the Study Eye on the Diabetic Retinopathy Severity Scale (DRSS) at Week 12	7-field or modified 4-field digital fundus photographs was obtained from both eyes by a qualified person according to the imaging manual to collect all data for the assessment of the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS). The images was sent to the independent central reading center who performs the grading on the basis of the DRSS. The DRSS ranges from level 10 (Diabetic retinopathy absent) to level 85 (advanced proliferative Diabetic retinopathy).	At baseline and at Week 12.
Secondary	Percentage of Participants With Adverse Events Other Than Ocular Adverse Events Over On-treatment Period	Percentage of participants with adverse events other than ocular adverse events over on-treatment period was reported.	On-treatment period: from first dose of study drug until end of follow-up period, up to 24 weeks.

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