E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Macular edema secondary to CRVO |
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E.1.1.1 | Medical condition in easily understood language |
Retinal venous occlusive disease is an important cause of vision loss, particularly in patients with associated chronic macular edema. |
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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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025415 |
E.1.2 | Term | Macular oedema |
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 determine the efficacy and durability (treatment interval) of 2 mg IVT aflibercept in a T&E regimen over a treatment period of 76 weeks using protocol defined visual and anatomic criteria in subjects with macular edema secondary to CRVO |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of IVT aflibercept as measured by visual acuity and anatomic outcomes using spectral domain optical coherence tomography (SD OCT), and perfusion status using FA/fundus photography (FP) and also to assess T&E applied posology of IVT aflibercept (number of injections, length of injection interval) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Center-involved macular edema secondary to CRVO for no longer than 3 months (at the screening visit it should be ensured that the subjects will comply with the criterion of ≤ 3 months since onset of macular edema at their scheduled baseline visit). - Adult subjects diagnosed with macular edema secondary to CRVO who are scheduled to be treated with IVT aflibercept as per investigator's routine treatment practice with the intent to use a T&E regimen after initial dosing. - Treatment-naïve subjects for macular edema secondary to CRVO. - Men and women ≥ 18 years of age. - Documented BCVA of ETDRS letter score of 73 to 24 letters (Snellen equivalent of 20/40 to 20/320) in the study eye. - Subject is willing, committed, and able to return for all clinic visits and complete all study-related procedures. - Women and men of reproductive potential must agree to use adequate contraception when sexually active. This applies for the time period between signing of the ICF and 3 months after the last administration of study drug. The definition of adequate contraception will be based on the judgment of the investigator and on local requirements. Acceptable methods of contraception include, but are not limited to, (i) condoms (male or female) with or without a spermicidal agent; (ii) diaphragm or cervical cap with spermicide; (iii) intra-uterine device; (iv) hormone-based contraception. Subjects must agree to utilize two reliable and acceptable methods of contraception simultaneously. - Negative pregnancy test (women of childbearing potential only |
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E.4 | Principal exclusion criteria |
- Previous PRP or macular laser photocoagulation in the study eye. - Any prior or concomitant ocular treatment (e.g. anti-VEGF therapy, corticosteroids) in the study eye for macular edema secondary to RVO, except dietary supplements or vitamins prior to inclusion in the study. Intraocular anti-VEGF treatment is permitted for the treatment of diseases of fellow eye except for those that are specifically excluded. - Prior systemic anti-VEGF or corticosteroid therapy, investigational or approved, within the last 3 months before the first dose in the study. - Previous use of intraocular corticosteroids in the study eye at any time or use of periocular corticosteroids in the study eye within 12 months prior to Day 1. - Any active intraocular, extraocular, and periocular inflammation or infection in either eye within 4 weeks of screening. - Any history of allergy to povidone iodine. - Known serious allergy to the fluorescein sodium for injection in angiography. - Presence of any contraindications indicated in the EU commission/locally approved label for IVT aflibercept: hypersensitivity to the active substance IVT aflibercept or to any of the excipients; active or suspected ocular or periocular infection; active severe intraocular inflammation. - A history of vitreoretinal surgery in the study eye prior to Day 1 (Visit 2) or anticipated within the 18 months following Day 1. - Iris neovascularization, neovascularization or fibrosis of the iridocorneal angle, or vitreous hemorrhage in the study eye. - History of vitreomacular traction in either the study eye or the fellow eye evident by biomicroscopic or OCT assessment that is considered by the investigator to affect central vision significantly. - History of retinal detachment or treatment or surgery for retinal detachment in the study eye. - Any history of macular hole of stage 2 and above in the study eye. - Prior trabeculectomy or other filtration surgery in the study eye. - Uncontrolled glaucoma (defined as IOP more than 25 mm Hg despite treatment with antiglaucoma medication) in the study eye. - Aphakia or pseudophakia with absence of posterior capsule (unless it occurred as a result of an yttrium aluminum garnet posterior capsulotomy) in the study eye. - Previous therapeutic radiation in the region of the study eye. - History of corneal transplant or corneal dystrophy in the study eye. - Significant media opacities, including cataract, in the study eye that interfere with visual acuity or FP. - History or clinical evidence of diabetic macular edema, AMD (neovascular AMD or geographic atrophy), BRVO, or any retinal vascular disease other than macular edema secondary to CRVO in either eye. - Any history of uveitis in either eye. - Presence of scleromalacia in either eye. - Pregnancy or breastfeeding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) The proportion of subjects who gain ≥ 15 letters in best corrected visual acuity on the early treatment diabetic retinopathy score chart.
2) The proportion of subjects with a mean treatment interval between injections of ≥ 8 weeks |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) Compared with baseline at Week 76
2) From the last actual visit of the initiation phase to Week 76 |
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E.5.2 | Secondary end point(s) |
1) The change in best corrected visual acuity as measured by the early treatment diabetic retinopathy letter score 2) The change in central retinal thickness 3) The number of injections 4) The mean treatment interval between injections 5) The proportion of subjects who gain ≥ 15 letters in best corrected visual acuity on the early treatment diabetic retinopathy chart 6) The change in retinal perfusion (FA/FP) status 7) The proportion of subjects with absence of fluid 8) Number and severity of ocular safety events detected by tonometry, indirect ophthalmoscopy, slit lamp biomicroscopy, and gonioscopy |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) From baseline to Weeks 24, 52, and 76 2) From baseline to Weeks 24, 52, and 76 3) From baseline to Week 76 4) From baseline to Week 76 5) Compared with baseline at Weeks 24 and 52 6) From baseline to Weeks 24, 52 and 76 7) At Weeks 24, 52, and 76 8) 30 days after week 76 |
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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 | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 |
Australia |
Canada |
Denmark |
France |
Germany |
Italy |
Spain |
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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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
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 | 9 |