E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
wet age-related macular degeneration (wAMD) |
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E.1.1.1 | Medical condition in easily understood language |
eye disease called wet age-related macular degeneration (wAMD) SRD part, MRD cohort1: treatment-resistant patients MRD cohort2: treatment-naive patients MRD cohort3: frequently treated patients |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064930 |
E.1.2 | Term | Age-related macular degeneration |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10075568 |
E.1.2 | Term | Wet age-related macular degeneration |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10075718 |
E.1.2 | Term | Exudative age-related macular degeneration |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the safety, tolerability and pharmacodynamics of single and multiple intravitreal doses of BI 836880. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
SRD part and MRD cohort 1 (treatment-resistant patients with wAMD): - Men and women over the age of 55 with active CNV secondary to AMD despite anti-VEGF therapies (at least 3 prior injections with the last injection within 16 to 4 weeks before treatment). - For MRD cohort 1 only: Central subfield retinal thickness >300 microns in the study eye. - 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. - 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 6/12 and 6/9.5) 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.
MRD cohort 2 (treatment-naive patients with wAMD): - 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 best-corrected VA.
MRD cohort 3 (frequently treated patients): - 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
All trial parts: - No subretinal hemorrhage involving the fovea in the study eye. - No subfoveal fibrosis or atrophy on SD-OCT in the study eye. - Female subjects must be of non-childbearing potential.
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E.4 | Principal exclusion criteria |
- Additional eye disease in the study eye that could compromise best corrected VA (BCVA) with visual field loss, uncontrolled glaucoma (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. - Active intraocular inflammation in the study eye, > 0.5+ anterior chamber cell and/or vitreous haze grading, or history of intraocular inflammation in either eye with previous IVT administration(s) (anterior chamber/haze grading and intraocular imflammation history only applicable to MRD cohort 3) - Active infectious conjunctivitis in either eye. - Participation in trials: - Previous participation in this trial. - Previous participation in other trials for treatment of wAMD with systemic administration if washout period from last administration is shorter than 3 months. - MRD cohort 1 & 3: Previous participation in other trials for treatment of wAMD with IVT injections in the study eye if washout period from last administration/injection is shorter than 3 months (IVT injections allowed if fellow eye was treated). - MRD cohort 2: No previous IVT injections for wAMD in the study eye (IVT injections allowed if fellow eye was treated). - Symptoms of active SARS-CoV-2 infection - Any history of retinal vein occlusion in the study eye (only applicable to MRD cohort 3). - Any previous treatment with brolucizumab or faricimab in either eye (only applicable to MRD cohort 3). - Medical history of autoimmune disease that has caused ocular inflammation (only applicable to MRD cohort 3). |
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E.5 End points |
E.5.1 | Primary end point(s) |
SRD Part: - Number of patients with ocular dose limiting events (DLEs).
MRD Part: - Number of patients with drug related AEs. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
SRD Part: 7 days after Primary Treatment
MRD Part: After EOT |
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E.5.2 | Secondary end point(s) |
SRD Part: - Number of patients with drug related AEs - Number of patients with any ocular AEs in the study eye
MRD Part: - Percent change from baseline in Central Subfield Thickness (CSFT) in the study eye at week 12, for each dose - Change from baseline in BCVA in the study eye at week 12 - Time to recurrence after the last treatment - Number of patients with any ocular AEs in the study eye
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
SRD Part: - week 12
MRD Part: - week 12 - last treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Safety Study for new route of administration (IVT) |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is defined as the date of the last visit of the last patient in the whole trial (Last Patient Out (LPO)). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |