A Study to Test Different Doses of BI 836880 in Patients With an Eye Disease Called Wet Age-related Macular Degeneration (wAMD)

Safety, Tolerability and Pharmacodynamics of Single Rising Intravitreal and Multiple Rising Intravitreal Doses of BI 836880 in Patients With wAMD (Open Label, Non-randomized, Uncontrolled).

This is a study in people with an eye disease called wet age-related macular degeneration (wAMD). The purpose of the study is to find out how well different doses of a medicine called BI 836880 are tolerated.

People can participate if they are at least 55 years old and if they have new blood vessels in their eyes despite treatment (anti-VEGF therapies). The study has 2 parts. In the first part, people get only 1 dose of BI 836880. This part takes 6 weeks. In the second part, people get 3 times the same dose of BI 836880. This part takes 6 months. BI 836880 is injected into the eye. During the entire study doctors regularly check the health of the participants.

Study Overview

• Status: Completed
• Conditions: Wet Macular Degeneration
• Intervention / Treatment: Drug: BI 836880

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12200
    • Charité - Universitätsmedizin Berlin
  • Göttingen, Germany, 37075
    • Universitätsmedizin Göttingen, Georg-August-Universität
  • Ulm, Germany, 89075
    • Universitätsklinikum Ulm
• United Kingdom
  • Bristol, United Kingdom, BS1 2LX
    • Bristol Eye Hospital
  • Liverpool, United Kingdom, L7 8XP
    • Royal Liverpool University Hospital
  • London, United Kingdom, EC1V 2PD
    • Moorfields Eye Hospital
  • Sunderland, United Kingdom, SR2 9HP
    • Sunderland Eye Infirmary
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants, Ltd.
  • New York
    • New York, New York, United States, 10003
      • New York Eye and Ear Infirmary of Mount Sinai
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Verum Research, LLC
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Erie Retina Research, LLC
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Austin, Texas, United States, 78750
      • Austin Clinical Research, LLC
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

SRD part and MRD cohort 1 (treatment-resistant patients with wAMD):

• Men and women over the age of 55 with active Choroidal Neovascularisation (CNV) secondary to age-related macular degeneration (AMD) despite anti-Vascualr endothelial growth factor (VEGF) therapies (at least 3 prior injections with the last injection within 16 to 4 weeks before treatment). Active CNV secondary to AMD is to be defined either by recent fluorescein or optical coherence tomography (OCT) angiogram within 4 weeks prior to screening or fluorescein or OCT angiogram obtained prior to first anti VEGF-treatment to confirm the diagnosis and still active according to investigator judgement.
• For MRD part only: Central subfield retinal thickness >300 microns in the study eye on Heidelberg Spectralis Spectral Domain Optical Coherence Tomography (SD-OCT).
• Presence of sub- and/or intraretinal fluid on SD-OCT in the study eye.
• Any active CNV with subfoveal leakage in the study eye as determined by OCT
• No subretinal hemorrhage involving the fovea in the study eye.
• No significant subfoveal fibrosis or atrophy on SD-OCT in the study eye that, in the opinion of the investigator, is able to prevent improvement in best corrected visual acuity (BCVA) and/or central subfield thickness (CSFT).
• Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) VA in the study eye between 75 and 24 letters inclusive (approximately 20/32 and 20/320 or 6/9.5 and 6/95) at screening.
• Best-corrected VA in the non-study eye better than best-corrected VA in the study-eye. If both eyes are eligible and have identical VA the investigator may select the study eye.
• Male or female patients. Women of childbearing potential (WOCBP) cannot be included. Men able to father a child must be ready and able to use highly effective methods 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 informed consent consistent with ICH GCP guidelines and local legislation prior to participation in the trial, which includes medication washout and restrictions.
• Not under any administrative or legal supervision or under institutionalization due to regulatory or juridical order.

MRD cohort 2 (treatment-naive patients with wAMD):

• No subretinal hemorrhage involving the fovea in the study eye.
• No significant subfoveal fibrosis or atrophy on SD-OCT in the study eye that, in the opinion of the investigator, is able to prevent improvement in BCVA and/or CSFT.
• Male or female patients. Women of childbearing potential (WOCBP) cannot be included. Men able to father a child must be ready and able to use highly effective methods 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 informed consent consistent with ICH GCP guidelines and local legislation prior to participation in the trial, which includes medication washout and restrictions.
• Not under any administrative or legal supervision or under institutionalization due to regulatory or juridical order.
• Men and women over the age of 55 with treatment-naïve CNV secondary to AMD.
• Any CNV with subfoveal activity in the study eye defined as evidence of sub- and/or intraretinal fluid, or subretinal hyper-reflective material, or angiographic leakage.
• Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) VA in the study eye between 80 and 24 letters inclusive (approximately 20/25 and 20/320 or 6/7.5 and 6/95) at screening.
• Best-corrected ETDRS VA in the non-study eye 50 letters inclusive (approximately 20/100 or 6/30) or better at screening.
• If both eyes are eligible at screening, the study eye is the eye with the worse bestcorrected VA.

MRD cohort 3 (frequently treated patients):

• No subretinal hemorrhage involving the fovea in the study eye.
• No significant subfoveal fibrosis or atrophy on SD-OCT in the study eye that, in the opinion of the investigator and with the endorsement of the Sponsor, is able to prevent improvement in BCVA.
• Male or female patients. Women of childbearing potential (WOCBP)1 cannot be included.Men able to father a child must be ready and able to use highly effective methods 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 informed consent consistent with ICH GCP guidelines and local legislation prior to participation in the trial, which includes medication washout and restrictions.
• Not under any administrative or legal supervision or under institutionalization due to regulatory or juridical order.
• Any CNV with subfoveal activity in the study eye defined as evidence of sub- and/or intraretinal fluid, or subretinal hyper-reflective material, or angiographic leakage.
• Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) VA in the study eye between 80 and 24 letters inclusive (approximately 20/25 and 20/320 or 6/7.5 and 6/95) at screening.
• If both eyes are eligible at screening, the study eye is the eye with the worse bestcorrected VA.

• Men and women over the age of 55 with diagnosed wAMD that:

  • require frequent wAMD SoC (28-56 days between the last 3 treatments)
  • have had ≥ 3 previous treatments with IVT SoC (ranibizumab, aflibercept, or bevacizumab) in the study eye
  • had the last SoC injection ≥ 4 weeks, but no more than 8 weeks, before the first administration of the study drug
  • have been on SoC treatment ≥ 6 months and are within 3 years from initial wAMD diagnosis in the study eye

Exclusion criteria:

• Additional eye disease in the study eye that could compromise best corrected VA (BCVA) with visual field loss, uncontrolled glaucoma (intraocular pressure (IOP)> 24 mmHg on more than 2 consecutive measurements prior to screening), clinically significant diabetic maculopathy, history of ischemic optic neuropathy or retinalvascular 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.
• Any prior intraocular surgery in the study eye other then uneventful lens replacement for cataract within 3 months prior to screening.
• Aphakia or total absence of the posterior capsule. Yttrium aluminum garnet (YAG) laser capsulotomy permitted, more than 1 month prior to enrollment in the study eye.
• Current or planned use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol).
• Medical history or condition: Uncontrolled diabetes mellitus, with hemoglobin A1c (HbA1c) > 10%, myocardial infarction or stroke within 12 months of screening, active bleeding disorder, concomitant use of warfarin or anticoagulation therapy (use of antiplatelet therapy such as aspirin is allowed), major surgery within 1 month of screening or when planned within the study period, hepatic impairment, uncontrolled hypertension.
• Patients with a clinically relevant abnormal screening haematology, blood chemistry, or urinalysis, if the abnormality defines a significant disease as defined in other exclusion criteria. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2.0-fold the upper limit of normal at screening. Patients with total bilirubin 2.5x upper limit of normal at screening.
• Patient with impaired renal function defined as calculated glomerular filtration rate (GFR) < 30 mL/min.
• Significant alcohol or drug abuse within past 2 years per investigator judgement.
• Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.06 mg BI 836880 - SRD part	Drug: BI 836880; Solution for Intravitreal (IVT) injection
Experimental: 0.18 mg BI 836880 - SRD part	Drug: BI 836880; Solution for Intravitreal (IVT) injection
Experimental: 0.5 mg BI 836880 - SRD part	Drug: BI 836880; Solution for Intravitreal (IVT) injection
Experimental: 1 mg BI 836880 - SRD part	Drug: BI 836880; Solution for Intravitreal (IVT) injection
Experimental: 2 mg BI 836880 - SRD part	Drug: BI 836880; Solution for Intravitreal (IVT) injection
Experimental: 1 mg BI 836880 - cohort 1 MRD part	Drug: BI 836880; Solution for Intravitreal (IVT) injection
Experimental: 2 mg BI 836680 - cohort 2 MRD part	Drug: BI 836880; Solution for Intravitreal (IVT) injection
Experimental: 2 mg BI 836680 - cohort 3 MRD part	Drug: BI 836880; Solution for Intravitreal (IVT) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SRD-part: Number of Participants With Ocular Dose Limiting Events (DLEs)	Single rising dose (SRD)-part: Number of participants with ocular dose limiting events (DLEs).	From drug administration until the end of trial (EOT) visit in the SRD part, up to 6 weeks.
MRD-part: Number of Participants With Drug Related Adverse Events (AEs)	Multiple rising dose (MRD)-part: Number of participants with drug related adverse events (AEs)	From first drug administration until the end of trial (EOT) visit in the MRD part, up to 24 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SRD-part: Number of Participants With Drug Related Adverse Events (AEs)	Single rising dose (SRD)-part: Number of participants with drug related adverse events (AEs).	From drug administration until the end of trial (EOT) visit in the SRD part, up to 6 weeks.
SRD-part: Number of Participants With Any Ocular Adverse Events in the Study Eye	Single rising dose (SRD)-part: Number of participants with any ocular adverse events in the study eye.	From drug administration until the end of trial (EOT) visit in the SRD part, up to 6 weeks.
MRD-part: Percentage Change From Baseline in Central Subfield Thickness (CSFT) in the Study Eye at Week 12	Multiple rising dose (MRD)-part: Central subfield thickness was measured using Spectral domain-optical coherence tomography (SD-OCT) with the assessment performed by a qualified person and only specified OCT equipment was used. Optical coherence tomography angiography (OCT-A), a non-invasive imaging technique providing high-resolution volumetric blood flow information without the use of dye was also performed by a qualified person, and only specified device(s) were used. OCT images were sent to an independent CRC for evaluation. A detailed manual for OCT image acquisition and data transmission was provided. CSFT was investigated after 3 doses of BI 836880 in the MRD part of the trial at Week 12.	At baseline and at week 12.
MRD-part: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye at Week 12	Multiple rising dose (MRD)-part): Visual acuity (VA) measured by 'early treatment diabetic retinopathy study' letter charts. BCVA was measured using the early treatment diabetic retinopathy study (ETDRS) VA chart starting at a test distance of 4 m. The BCVA score was the number of letters read correctly by the patient. The assessment was performed by a trained person under specified conditions regarding examination room and equipment.	At baseline and at Week 12.
MRD-part: Time to Recurrence in the Study Eye From Last Administration at Each Visit	Multiple rising dose (MRD)-part: Time to recurrence was assessed in the MRD part from last trial drug administration to occurrence of any of the following in the study eye, leading to the use of wet age-related macular degeneration (wAMD) rescue medication as decided by the investigator: Increase in Central Subfield Thickness (CFST) ≥75 μm with a decrease in Best Corrected Visual Acuity (BCVA) of ≥ 5 letters compared to Visit 5, OR; Decrease in BCVA of >5 letters compared to baseline (Visit 2), due to worsening wAMD activity, OR; Decrease in BCVA of ≥10 letters compared to the best prior BCVA, due to worsening wAMD activity From above criteria, if Visit 5 BCVA/CSFT assessment data is missing, BCVA/CSFT values available earlier than Visit 5 will be used. The last trial drug administration is strictly referring to the third injection, if a patient doesn't complete three injections, the patient will not be evaluated for time to recurrence endpoint and will be censored.	From last drug administration at Week 8 until End of Trial, up to 16 weeks.
MRD-part: Number of Participants With Any Ocular Adverse Events in the Study Eye	Multiple rising dose (MRD)-part: Number of participants with any ocular adverse events in the study eye.	From first drug administration until the end of trial (EOT) visit in the MRD part, up to 24 weeks.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2019
• Primary Completion (Actual): November 1, 2023
• Study Completion (Actual): November 1, 2023

Study Registration Dates

• First Submitted: February 26, 2019
• First Submitted That Met QC Criteria: March 1, 2019
• First Posted (Actual): March 4, 2019

Study Record Updates

• Last Update Posted (Actual): November 20, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Wet Macular Degeneration
• Other Study ID Numbers: 1336-0007; 2017-001221-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datasharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No