E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic macular edema with central involvement |
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E.1.1.1 | Medical condition in easily understood language |
Patients with water retention in the back of the eye as a result of diabetes mellitus |
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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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057934 |
E.1.2 | Term | Diabetic macular edema |
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 |
To assess the efficacy of intravitreally (IVT) administered VEGF Trap Eye in comparison to laser treatment in improving best corrected visual acuity (BCVA) in subjects with diabetic macular edema (DME) with central involvement |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of IVT administered VEGF Trap Eye in subjects with DME |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetic sub-study for the the collection of blood samples for DNA analyses. |
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E.3 | Principal inclusion criteria |
1. Adults ≥ 18 years with type 1 or 2 diabetes mellitus.
2. Subjects with DME secondary to diabetes mellitus involving the center of
the macula (defined as the area of the center subfield of optical coherence tomography [OCT]) in the study eye.
3. Decrease in vision determined to be primarily the result of DME in the study eye
4. Retinal thickness as assessed by OCT of ≥300 µm in the study eye.
5. BCVA ETDRS letter score of 73 to 24 (20/40 to 20/320) in the study eye.
6. Willing and able to comply with clinic visits and study-related procedures.
7. Provide a signed informed consent form (ICF). In Japan only, the informed consent form for a subject under the age of 20 years will require the co-signature of the subject’s legally authorized representative.
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E.4 | Principal exclusion criteria |
1. Ocular conditions with a poorer prognosis in the fellow eye than in the study eye.
2. History of vitreoretinal surgery and/or including scleral buckling in the study eye
3. Laser photocoagulation (panretinal or macular) in the study eye within 90 days of Day 1
4. More than 2 previous macular laser treatments in the study eye or, in the opinion of the investigator, the subject has no potential to benefit from laser treatments (eg, if too many laser treatments were applied in the past).
5. Previous use of intraocular or periocular corticosteroids in the study eye within 120 days of Day 1
6. Previous treatment with anti-antiangiogenic drugs in either eye (pegaptanib sodium, bevacizumab, ranibizumab etc.) within 90 days of Day 1
7. Active, proliferative diabetic retinopathy (PDR) in the study eye, with the exception of inactive, regressed PDR
8. History of idiopathic or autoimmune uveitis in the study eye
9. Cataract surgery within 90 days before Day 1 in the study eye
10. Aphakia in the study eye
11. Yttrium-aluminium-garnet (YAG) capsulotomy in the study eye within 30 days before Day 1
12. Any other intraocular surgery within 90 days of Day 1 in the study eye
13. Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or on OCT that is thought to affect central vision
14. Current iris neovascularization, vitreous hemorrhage, or tractional retinal detachment in the study eye
15. Pre-retinal fibrosis involving the macula in the study eye
16. Structural damage to the center of the macula in the study eye that is likely to preclude improvement in BCVA following the resolution of macular edema including atrophy of the retinal pigment epithelium, subretinal fibrosis or scar, significant macular ischemia or organized hard exudates.
17. Ocular inflammation including trace or above in the study eye
18. Evidence of infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye
19. Filtration surgery for glaucoma in the past or likely to be needed in the future on the study eye
20. Intraocular pressure (IOP) ≥ 25 mmHg in the study eye
21. Myopia of a spherical equivalent prior to any possible refractive or cataract surgery of ≥ 8 diopters
22. Concurrent disease in the study eye, other than DME, that could compromise VA, require medical or surgical intervention during the study period, or could confound interpretation of the results (including retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause)
23. Only 1 functional eye even if that eye is otherwise eligible for the study
24. Ocular media of insufficient quality to obtain fundus and OCT images
25. Current treatment for a serious systemic infection
26. Administration of systemic anti-angiogenic agents within 180 days before Day 1
27. Uncontrolled diabetes mellitus, as defined by HbA1c >12%.
28. Uncontrolled blood pressure (defined as systolic >160 mmHg or diastolic >95 mmHg while subject is sitting)
29. History of either cerebral vascular accident and/or myocardial infarction within 180 days prior to Day 1
30. Renal failure requiring dialysis or renal transplant
31. 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 an investigational drug, might affect interpretation of the results of the study, or renders the subject at high risk for treatment complications.
32. Pregnant or breast-feeding women. In addition, to prevent exposure during pregnancy female subjects, male subjects, and their partners must agree to the following.
33. Women of childbearing potential with either a positive pregnancy test result or no pregnancy test at baseline are excluded. Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential.
34. Sexually active men or women of childbearing potential who are unwilling to practice adequate contraception during the study are excluded. (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly or diaphragm plus contraceptive sponge, foam, or jelly)
35. Allergy to fluorescein
36. Participation in an investigational study within 30 days prior to screening visit that involved treatment with any drug (excluding vitamins and minerals) or device.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change from baseline of BCVA in ETDRS letters score at Week 52 compared to baseline (Day 1). |
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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) |
Comparisons between each of the VEGF Trap-Eye arms and the laser arm
on the secondary efficacy endpoints will be performed only when the
respective VEGF Trap-Eye arm demonstrates statistically significant
difference from laser arm on the primary endpoint at week 52. To control
the type I error, the secondary endpoints will be tested sequentially in
the order described below:
-Proportion of subjects who gain >/= 10 ETDRS letters from baseline
to week 52
-Proportion of subjects who gain >/= 15 ETDRS letters from baseline
to week 52 (as of Amd 2)
-Proportion of subjects whith a >/= two-step improvement from baseline to Week 52 in the ETDRS diabetic retinopathy (DR) severity scale, as assessed by FP. (as of Amd 2)
-Change in CRT from baseline to Week 52, as assessed on OCT.
-NEI VFQ-25 near activities subscale change from baseline to Week 52
-NEI VFQ-25 distance activities subscale change from baseline to Week
52 |
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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 | Yes |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
macular laser photocoagulation |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 | Information not present in EudraCT |
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 |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |