| Eligibility |
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.
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