Clinical trial NCT03861234: A Study to Test Different Doses of BI 836880 in Patients With an Eye Disease Called Wet Age-related Macular Degeneration (wAMD)
Official title: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Wet Macular Degeneration
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2019-03-04
Enrollment: 43
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: SRD-part: Number of Participants With Ocular Dose Limiting Events (DLEs)
timeFrame: From drug administration until the end of trial (EOT) visit in the SRD part, up to 6 weeks.
measure: MRD-part: Number of Participants With Drug Related Adverse Events (AEs)
timeFrame: From first drug administration until the end of trial (EOT) visit in the MRD part, up to 24 weeks.
Secondary outcomes:
measure: SRD-part: Number of Participants With Drug Related Adverse Events (AEs)
timeFrame: From drug administration until the end of trial (EOT) visit in the SRD part, up to 6 weeks.
measure: SRD-part: Number of Participants With Any Ocular Adverse Events in the Study Eye
timeFrame: From drug administration until the end of trial (EOT) visit in the SRD part, up to 6 weeks.
measure: MRD-part: Percentage Change From Baseline in Central Subfield Thickness (CSFT) in the Study Eye at Week 12
timeFrame: At baseline and at week 12.
measure: MRD-part: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye at Week 12
timeFrame: At baseline and at Week 12.
measure: MRD-part: Time to Recurrence in the Study Eye From Last Administration at Each Visit
timeFrame: From last drug administration at Week 8 until End of Trial, up to 16 weeks.
measure: MRD-part: Number of Participants With Any Ocular Adverse Events in the Study Eye
timeFrame: From first drug administration until the end of trial (EOT) visit in the MRD part, up to 24 weeks.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Associated Retina Consultants, Ltd.
state: Arizona
city: New York
country: United States
facility: New York Eye and Ear Infirmary of Mount Sinai
state: New York
city: Eugene
country: United States
facility: Verum Research, LLC
state: Oregon
city: Erie
country: United States
facility: Erie Retina Research, LLC
state: Pennsylvania
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Austin
country: United States
facility: Austin Clinical Research, LLC
state: Texas
city: Bellaire
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen, Georg-August-Universität
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Bristol
country: United Kingdom
facility: Bristol Eye Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
city: Sunderland
country: United Kingdom
facility: Sunderland Eye Infirmary
Study officials:
References: