E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Maculare edema secondary to Central Retinal Vein Occlusion |
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E.1.1.1 | Medical condition in easily understood language |
Fluid retention in the central spot of the retina, as a consequence of a clotting of the central blood vessel in the eye. |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054467 |
E.1.2 | Term | Macular edema |
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007972 |
E.1.2 | Term | Central retinal vein occlusion |
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 of intravitreally (IVT) administered VEGF Trap-Eye on best-corrected visual acuity (BCVA) assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart in subjects with macular edema secondary to CRVO. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of IVT administered VEGF Trap-Eye in subjects with macular edema secondary to CRVO.
To assess the effects of IVT administered VEGF Trap-Eye on central retinal thickness (CRT) in subjects with macular edema secondary to CRVO.
To assess the pharmacokinetics of free and bound VEGF Trap in a subset of patients.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Center-involved macular edema secondary to CRVO for no longer than 9 months with mean central subfield thickness ≥ 250 μm on OCT.
2. Adults ≥ 18 years.
3. ETDRS BCVA of 20/40 to 20/320 (73 to 24 letters) in the study eye.
4. For men and women of childbearing potential, willingness to utilize adequate contraception and not become pregnant (or have their partner[s] become pregnant) during the full course of the study. Adequate contraceptive measures include oral contraceptives (stable use for 2 or more cycles prior to screening) and other prescription pharmaceutical contraceptives, intrauterine device (IUD), bilateral tubal ligation, vasectomy, condom, or diaphragm plus either contraceptive sponge, foam, or jelly.
5. Willing, committed, and able to return for ALL clinic visits and complete all study-related procedures.
6. Willingness to provide written informed consent.
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E.4 | Principal exclusion criteria |
1. Only one functional eye even if that eye is otherwise eligible for the study. Furthermore, subjects with only one eligible eye should not have other ocular conditions with poorer prognosis in the fellow eye.
2. Any prior or concomitant ocular (in the study eye) treatment or surgery for macular edema secondary to CRVO, or systemic use of anti-VEGF products
3. Any prior or concomitant therapy with another investigational agent to treat macular edema secondary to CRVO in the study eye.
4. Any prior treatment with anti-VEGF agents in the study eye or previous administration of systemic anti-gngiogenic medications.
5. Previous use of intraocular corticosteroids in the study eye at any time or use of periocular corticosteroids in the study eye within 3 months prior to Day 1.
6. Previous use of intraocular or periocular corticosteroids in the fellow eye within 3 months prior to Day 1.
7. History of vitreoretinal surgery in the study eye prior to Day 1 (Visit 2) or anticipated within the 12 months following Day 1.
8. Bilateral manifestation of RVO.
9. History of radial optic neurotomy or sheathotomy.
10. Previous pan-retinal laser photocoagulation or macular laser photocoagulation in the study eye.
11. Decrease in BCVA due to causes other than CRVO.
12. History or presence of AMD (dry or wet form) that is considered by the investigator to significantly affect central vision, DME, or diabetic retinopathy defined as more than one microaneurysm outside the area of the vein occlusion in diabetic subjects in either the study eye or the fellow eye.
13. Iris neovascularization, vitreous hemorrhage, traction retinal detachment, or preretinal fibrosis involving the macula in either the study eye or the fellow eye.
14. Vitreomacular traction or epiretinal membrane in either the study eye or the fellow eye evident biomicroscopically or on OCT that is considered by the investigator to significantly affect central vision.
15. Ocular inflammation (including trace or above) or external ocular inflammation in the study eye.
16. History of idiopathic or autoimmune uveitis in either eye.
17. Structural damage to the center of the macula in either the study eye or the fellow eye that is likely to preclude improvement in visual acuity (VA) following the resolution of macular edema.
18. Concurrent disease in the study eye that would compromise VA or require medical or surgical intervention during the study period.
19. Cataract surgery in the study eye within 3 months, yttrium-aluminum-garnet laser capsulotomy within the past 2 months, or any other intraocular surgery within the 3 months prior to Day 1 (Visit 2).
20. Aphakia or absence of the posterior capsule in the study eye.
21. Uncontrolled glaucoma, defined as intraocular pressure (IOP) ≥ 25 mm Hg on optimal medical regimen, or previous filtration surgery in either the study eye or the fellow eye.
22. Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia (for subjects who have had refractive or cataract surgery in the study eye, preoperative spherical equivalent refractive error of more than -8 diopters myopia).
23. Evidence at examination of infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye or current treatment for serious systemic infection.
24. Any ocular disorders in the study eye that, in the opinion of the investigator, may confound interpretation of study results.
25. Uncontrolled hypertension defined as a single measurement of systolic > 180 mm Hg, two consecutive measurements of systolic > 160 mm Hg, or diastolic > 100 mm Hg on optimal medical regimen.
26. Uncontrolled diabetes mellitus.
27. History of cerebrovascular disease or myocardial infarction within 6 months prior to Day 1 (Visit 2).
28. Renal failure requiring dialysis or renal transplant.
29. Participation in an investigational study within 30 days prior to initial screening visit that involved treatment with any drug (excluding vitamins and minerals) or device.
30. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, might affect interpretation of the results of the study, or renders the subject at high risk from treatment complications.
31. Pregnancy or lactation.
32. History of allergy to fluorescein used in fluorescein angiography.
33. Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed by the site.
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects who gain at least 15 letters in BCVA on the EDTRS chart compared with baseline at the Week 24 endpoint. |
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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) |
Change from baseline in BCVA score [ Time Frame: Week 24 ]
Absolute change from baseline in central retinal thickness, assessed by OCT [ Time Frame: Week 24 ]
Proportion of subjects progressing to anterior segment neovascularization, neovascularization of the optic disc (NVD), or neovascularization of the retina elsewhere (NVE) requiring pan-retinal photocoagulation [ Time Frame: Week 24 ]
Change in the NEI-VFQ-25 total score from baseline [ Time Frame: Week 24 ]
Change in the EQ-5D score from baseline [ Time Frame: Week 24 ]
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | 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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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 | 22 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 |
Austria |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Latvia |
Singapore |
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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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End of trial is last visit of last subject. |
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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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |