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 | 19.1 |
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 | 19.1 |
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 functional changes in best corrected visual
acuity (BCVA) after 2 months (8 weeks) of treatment with FYB201 or
Lucentis, compared to baseline BCVA |
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E.2.2 | Secondary objectives of the trial |
Evaluate and compare functional changes of the retina by BCVA 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
Evaluate and compare change in vision-related functioning and well-being measured by NEI VFQ-25 at Months 6 and 12 compared to baseline
Evaluate and compare the immunogenic profile (anti-drug antibodies) in serum, local and systemic adverse events and serious adverse events |
|
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 or surgically sterile
5. Newly diagnosed, angiographically documented, primary active CNV lesion secondary to age-related macular degeneration (AMD)
6. Sufficiently clear ocular media and adequate pupillary dilation to permit good quality ocular imaging |
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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 prior 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 or periocular injections of 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in BCVA by ETDRS letters after 2 months (8
weeks) of treatment |
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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
• 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 over time
• Change from baseline in BCVA by ETDRS letters after 12 months
• 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
• 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 | 5 |
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 |
Poland |
Russian Federation |
Spain |
Ukraine |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 |