E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Visual impairment due to neovascular AMD |
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E.1.1.1 | Medical condition in easily understood language |
Impaired vision due to growth of new vessels (neovascularization) in the choroid which is caused by an intrinsic substance, so-called vascular endothelial growth factor (VEGF) |
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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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060837 |
E.1.2 | Term | Choroidal neovascularization |
E.1.2 | System Organ Class | 100000004853 |
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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 |
The primary objective of this study is to compare the treatment effect of ranibizumab PRN (BCVA loss and/or SD-OCT disease activity guided retreatment) versus aflibercept bimonthly regimen on CSRT stability as measured by mean CSRT fluctuations between study Month 3 and 6. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is as follows:
• To demonstrate correlation of functional outcome (BCVA) at month 12 with retinal stress, defined as significant fluctuations in central retinal thickness, parameters as measured by SD-OCT up to moth 6.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria for patient
1. Male or female patients, ≥ 18 years of age.
2. Written informed consent must be obtained before any study-related assessment is performed.
Inclusion criteria for study eye
3. Visual impairment predominantly due to neovascular AMD.
4. Active, newly diagnosed, untreated, angiographically documented, CNV lesion (i.e. leakage on fluorescein angiography plus intraretinal, subretinal or sub-RPE fluid on OCT) secondary to neovascular AMD in line with Summary of product characteristics of ranibizumab (Lucentis®) and aflibercept (Eylea®).
If both eyes are eligible for the study, the eye with the lower visual acuity will be defined as the study eye. This decision and confirmation needs to be documented in the electronic case report form (eCRF) and in the source documents of the patient. The study eye is the one treated with the study treatment, assessed according to protocol requirements and as outlined in the Assessment Schedule (Table 7-1) and data collected on the study eye are used for the evaluation of efficacy objectives of the study.
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E.4 | Principal exclusion criteria |
Exclusion criteria for patient
1. Inability to comply with study or follow-up procedures.
2. Women
o who are pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml))
o who are menstruating and capable of becoming pregnant and not practicing a medically approved method of contraception (Pearl Index <1) during and up to at least 4 weeks after the end of treatment. A negative pregnancy test (serum) for all women and for girls entering menarche is required with sufficient lead time before inclusion
Exclusion criteria for systemic medical history and conditions
3. Any type of systemic disease or its treatment, 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.
4. Stroke or myocardial infarction less than 3 months prior to screening.
5. Uncontrolled blood pressure defined as systolic value of >160 mm Hg or diastolic value of >100 mm Hg at screening or baseline.
6. History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures
Exclusion criteria for ocular medical history and conditions
For either eye
7. Any active periocular or ocular infection or inflammation (e.g., blepharitis, conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis) at the time of screening or baseline as per summary of product characteristics for both drugs.
8. Uncontrolled glaucoma (intraocular pressure [IOP] ≥30 mm Hg on medication or according to investigator’s judgment) at the time of screening or baseline.
9. Neovascularization of the iris or neovascular glaucoma at the time of screening or baseline.
10. Inability to obtain OCT images of sufficient quality to be analyzed.
For study eye
11. Cataract (if causing significant visual impairment), planned cataract surgery during the study period, aphakia, severe vitreous hemorrhage, rhegmatogenous retinal detachment, proliferative retinopathy or choroidal neovascularization of any other cause than wAMD (e.g., ocular histoplasmosis, pathologic myopia) at the time of screening and baseline.
12. Irreversible structural damage within 0.5 disc diameter of the center of the macula (e.g., vitreomacular traction, epiretinal membrane, scar, laser burn, macular hole) at the time of screening and baseline that in the investigator’s opinion could preclude visual function improvement with treatment.
13. Atrophy or fibrosis involving the center of the fovea.
Exclusion criteria for prior or current systemic medication
14. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
15. Use of any systemic anti-VEGF drugs (e.g., bevacizumab [Avastin®]).
16. Use of systemic or intravitreal corticosteroids for at least 30 consecutive days within 3 months prior to screening.
17. 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.
Exclusion criteria for prior or current ocular treatment
For either eye
18. Treatment with any anti-angiogenic drugs (including any anti-VEGF agents) prior to baseline in either eye (e.g., bevacizumab [Avastin®]).
For study eye
19. Any intraocular procedure (including Yttrium-Aluminum-Garnet capsulotomy) within 2 months prior to baseline or anticipated within the next 6 months following baseline.
20. Topical ocular corticosteroids administered for at least 30 consecutive days within 3 months prior to screening.
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E.5 End points |
E.5.1 | Primary end point(s) |
CSRT stability as measured by mean CSRT fluctuations between study Month 3 and 6. |
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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) |
Correlation of functional outcome (BCVA) at month 12 with retinal stress, defined as significant fluctuations in central retinal thickness, parameters as measured by SD-OCT up to moth 6.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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) | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 17 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |