E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subfoveal neovascular age-related macular degeneration |
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E.1.1.1 | Medical condition in easily understood language |
Age related macular degeneration |
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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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071129 |
E.1.2 | Term | Neovascular 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 | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067791 |
E.1.2 | Term | Wet 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 evaluate and compare changes in foveal center point (FCP) retinal thickness evaluated after 1 month (4 weeks) of treatment with FYB201 or Lucentis compared with baseline FCP retinal thickness |
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E.2.2 | Secondary objectives of the trial |
Evaluate and compare functional changes of the retina by BCVA at Month 6 (24 weeks) and over time Evaluate and compare changes in FCP retinal thickness and change in foveal central subfield retinal thickness over time Evaluate and compare presence of active choroidal neovascularization leakage at Month 6 and 12 compared to baseline Evaluate and compare the absence of disease activity (fluid-free macula) over time Evaluate and compare total lesion size at Month 6 and 12 compared to baseline Evaluate and compare systemic ranibizumab concentrations close to Cmax (24 h after the first dose) in a subgroup of 60 patients (30 per arm) Evaluate and compare change in vision-related functioning and well-being measured by National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) at Months 6 and 12 compared to baseline Evaluate and compare the immunogenic profile (anti-drug antibodies) in serum Evaluate and compare local and systemic adverse events and serious adverse events |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 50 years of either gender 2. Signed informed consent form must be obtained before any study-related procedure is performed 3. Willingness and ability to undertake all scheduled visits and assessments 4. Women must be postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (with documentation in the patient’s medical records) 5. Newly diagnosed, angiographically documented, primary active CNV lesion secondary to age-related macular degeneration (AMD) a. All subtypes of wet AMD CNV lesions are eligible (classic, occult, some classical component, retinal angiomatous proliferation lesions). Active primary CNV must be subfoveal or juxtafoveal with subfoveal component related to CNV activity (such as sub- or intraretinal fluid by spectral domain optical coherence tomography (SD-OCT) or retinal pigment epithelium (RPE) detachment) b. Total area of whole lesion must be equal or less than 12 disc areas c. Total CNV area encompasses equal or more than 50% of total lesion area based on fluorescein angiography (FA), including all subtypes of wet AMD 6. Sufficiently clear ocular media and adequate pupillary dilation to permit good quality ocular imaging 7. BCVA in the study eye, determined by standardized Early Treatment Diabetic Retinopathy Study (ETDRS) testing, between 20/32 (0.63) and 20/100 (0.2) Snellen equivalent 8. FCP retinal thickness at Screening ≥ 350 µm. (FCP thickness is defined as the distance between the vitreoretinal interface and Bruch’s membrane at the geometric center of the fovea) 9. BCVA in the fellow eye, determined by standardized ETDRS testing, at least 20/100 (0.2) Snellen equivalent |
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E.4 | Principal exclusion criteria |
1. Employees of clinical study sites, individuals directly involved with the conduct of the study or immediate family members thereof, prisoners, and persons who are legally institutionalized 2. Any previous treatment with IVT anti-vascular endothelial growth factor (VEGF) agent (e.g., bevacizumab, aflibercept, ranibizumab) in either eye 3. History of vitrectomy, macular surgery or other surgical intervention for AMD in the study eye 4. History of IVT treatment with corticosteroids or device implantation within six months prior to Screening in the study eye 5. Prior treatment with verteporfin (photodynamic therapy), transpupillary thermotherapy, radiation therapy, or retinal laser treatment (e.g. focal laser photocoagulation) in the study eye 6. Topical ocular corticosteroids administered for at least 30 consecutive days within three months prior to Screening 7. Any other intraocular surgery (including cataract surgery) in the study eye within three months prior to Screening 8. Sub- or intra-retinal hemorrhage that comprises more than 50% of the entire lesion in the study eye 9. Fibrosis or atrophy involving the center of the fovea or influencing central visual function in the study eye 10. CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia 11. Retinal pigment epithelial tear involving the macula in the study eye 12. History of full-thickness macular hole (stage 2 and above by clinical examination or full thickness macular hole by SD-OCT imaging of any size) in the study eye 13. History of retinal detachment in the study eye 14. Current vitreous hemorrhage in the study eye 15. Spherical equivalent of the refractive error in the study eye demonstrating more than 8 diopters of myopia 16. For patients who have undergone prior refractive or cataract surgery in the study eye, the preoperative refractive error in the study eye cannot exceed 8 diopters of myopia 17. History of corneal transplant in the study eye 18. Aphakia in the study eye. Absence of an intact posterior capsule is allowed if it occurred as a result of YAG laser posterior capsulotomy in association with prior posterior chamber intraocular lens (IOL) implantation 19. Active or recent (within 4 weeks) intraocular inflammation of clinical significance in the study eye such as active infections of the anterior segment (excluding mild blepharitis) including conjunctivitis, keratitis, scleritis, uveitis or endophthalmitis 20. Uncontrolled hypertension or glaucoma in the study eye (defined as intraocular pressure [IOP] ≥30 mm Hg, despite treatment with anti-glaucomatous medication) 21. Ocular disorders in the study eye (i.e. retinal detachment, pre-retinal membrane of the macula or cataract with significant impact on visual acuity) at the time of enrollment that may confound interpretation of study results and compromise visual acuity 22. Any concurrent intraocular condition in the study eye (e.g. glaucoma, cataract or diabetic retinopathy) that, in the opinion of the Investigator, would either require surgical intervention during the study to prevent or treat visual loss that might result from that condition or affect interpretation of study results. 23. Use of other investigational drugs (excluding vitamins, minerals) within 30 days or 5 half-lives from Screening, whichever is longer 24. Any type of advanced, severe or unstable disease, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk 25. Stroke or myocardial infarction within three months prior to Screening 26. Presence of uncontrolled systolic blood pressure > 160 mmHg or uncontrolled diastolic blood pressure > 100 mmHg 27. Known hypersensitivity to the investigational drug (ranibizumab or any component of the ranibizumab formulation) or to drugs of similar chemical class or to fluorescein or any other component of fluorescein formulation 28. Current or planned use of systemic medications known to be toxic to the lens, retina or optic nerve, including deferoxamine, chloroquine/hydroxychloroquine (Plaquenil®), tamoxifen, phenothiazines and ethambutol 29. History of recurrent significant infections and/or current treatment for active systemic infection 30. Pregnancy or lactation 31. Systemic treatment with long acting corticosteroids (more than 10 mg prednisolone equivalent) during the last six months prior to Screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the change from baseline FCP retinal thickness evaluated by SD-OCT. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints • Change from baseline in BCVA by ETDRS letters • Changes from baseline in FCP retinal thickness and FCS retinal thickness • Percentage of patients with active CNV leakage • Percentage of patients with fluid-free macula at each visit • Change from baseline in total lesion area • Systemic ranibizumab concentrations close to Cmax in a subgroup of 60 patients (30 per arm) • Change from baseline in vision-related functioning and well-being measured by NEI VFQ-25 • Number of patients with anti-ranibizumab antibodies • Frequency of local and systemic AEs and SAEs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Efficacy Endpoints • Change from baseline in BCVA by ETDRS letters at Month 6 (24 weeks) and over time • Changes from baseline in FCP retinal thickness and FCS retinal thickness over time • Percentage of patients with active CNV leakage at Month 6 and Month 12 • Percentage of patients with fluid-free macula at each visit • Change from baseline in total lesion area at Month 6 and Month 12 • Systemic ranibizumab concentrations close to Cmax (24 hours after the first dose) in a subgroup of 60 patients (30 per arm) • Change from baseline in vision-related functioning and well-being measured by NEI VFQ-25 at Month 6 and Month 12 • Number of patients with anti-ranibizumab antibodies over time |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
systemic ranibizumab concentrations close to Cmax (24 h after the first dose) in a subgroup of 60 patients (30 per arm) |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 75 |
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 |
Austria |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Netherlands |
Poland |
Russian Federation |
Spain |
United Kingdom |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
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 |