E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Macular Oedema due to Branch Retinal Vein Occlusion (BRVO) or Central Retinal Vein Occlusion (CRVO) |
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MedDRA Classification |
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 the safety and efficacy of the 700 µg DEX PS DDS Applicator System (700 µg dexamethasone) and 350 µg DEX PS DDS Applicator System (350 µg dexamethasone) compared with a Sham DEX PS DDS Applicator System (needle-less applicator) in patients with Macular Oedema due to Branch Retinal Vein Occlusion (BRVO) or Central Retinal Vein Occlusion (CRVO).
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E.2.2 | Secondary objectives of the trial |
To evaluate safety and efficacy of the 700 µg DEX PS DDS Applicator System (700 µg dexamethasone) compared with the 350 µg DEX PS DDS Applicator System (350 µg dexamethasone) in patients with Macular Oedema due to Branch Retinal Vein Occlusion (BRVO) or Central Retinal Vein Occlusion (CRVO) To assess the safety of the 700 µg DEX PS DDS Applicator System for an additional 6 months in patients who qualify for treatment in an open-label extension.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, at least 18 years of age 2. Macular edema in the study eye with all of the following characteristics: -involving the center of the macula (fovea) -due to BRVO or CRVO -with a duration of 6 weeks to 9 months prior to qualification/baseline visit for CRVO patients and a duration of 6 weeks to 12 months prior to qualification/baseline visit for BRVO patients -VA decrease attributable to the edema -in the investigator’s opinion, unlikely to be adversely affected if not treated for 6 months 3. BCVA score between 34 letters (approximately 20/200 Snellen equivalent) and 68 letters (approximately 20/50 Snellen equivalent) in the study eye measured by the ETDRS method at qualification/baseline 4. Retinal thickness of ≥ 300 µm by OCT in the central 1 mm macular subfield of the study eye at qualification/baseline as determined by the investigator 5. Female patients of childbearing potential must have a negative urine pregnancy test at the randomization (day 0) visit 6. Written informed consent has been obtained 7. Written Authorization for Use and Release of Health and Research Study Information (US sites only) has been obtained 8. Written Data Protection Consent (European sites only) has been obtained 9. Written documentation has been obtained, in accordance with state and country privacy requirements, where applicable |
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E.4 | Principal exclusion criteria |
1. Uncontrolled systemic disease 2. Any ocular condition in the study eye that, in the opinion of the investigator, would prevent a 15-letter improvement in visual acuity (eg, severe macular ischemia) 3. Presence of an epiretinal membrane in the study eye which, in the opinion of the investigator, is the primary cause of macular edema, or is severe enough to prevent improvement in visual acuity despite reduction in macular edema 4. History of IOP elevation in response to steroid treatment in either eye that resulted in any of the following: 1) a ≥ 10 mm Hg increase in IOP from baseline; 2) IOP ≥ 25 mm Hg; or 3) required therapy with anti-glaucoma medications 5. History of glaucoma or optic nerve head change consistent with glaucoma damage, and/or glaucomatous visual field loss in the study eye. Patients with a history of previous angle-closure that has been successfully treated with either a laser or surgical peripheral iridotomy (PI) are allowed as long as the visual fields have been stable for > 1 year prior to study entry and the patient has been and can be safely dilated. 6. Ocular hypertension in the study eye at qualification/baseline with any of the following: 1) IOP > 23 mm Hg if taking no anti-glaucoma medications; 2) IOP > 21 mm Hg if taking one anti-glaucoma medication; or 3) use of 2 or more anti-glaucoma medications (combination products should be considered 2 medications) Note: Anti-glaucoma medications or lack thereof must be stable for at least 4 weeks prior to qualification/baseline. 7. Aphakia or presence of anterior chamber intraocular lens in the study eye 8. Diabetic retinopathy in either eye 9. Active or history of choroidal neovascularization in the study eye 10. Presence of rubeosis iridis in the study eye at qualification/baseline 11. Any active ocular infection (ie, bacterial, viral, parasitic, or fungal) in either eye at qualification/baseline 12. History of herpetic infection in the study eye or adnexa 13. Presence of active or inactive toxoplasmosis in either eye at qualification/baseline 14. Presence of visible scleral thinning or ectasia in the study eye at qualification/baseline 15. Intraocular surgery, including cataract surgery, and/or laser of any type in the study eye within 90 days prior to qualification/baseline 16. History of central serous chorioretinopathy in either eye 17. History of pars plana vitrectomy in the study eye 18. History of use of intravitreal steroids or any intravitreal injectable drug in the study eye 19. Periocular depot of steroids to the study eye within 6 months prior to qualification/baseline 20. Use of systemic steroids (e.g., oral, intravenous, intra-articular, epidural, intrabursal) within 1 month prior to qualification/baseline visit or anticipated use at any time during the study. Inhaled and intranasal steroids are allowed. 21. Use of topical or systemic carbonic anhydrase inhibitors (e.g., Azopt®, Trusopt®, Diamox®) within 1 month prior to qualification/baseline visit or anticipated use at any time during the study 22. Use of immunosuppressants, immunomodulators, antimetabolites, and/or alkylating agents use within 6 months prior to qualification/baseline or anticipated use at any time during the study 23. Use of topical ophthalmic steroids or topical non-steroidal anti-inflammatory drugs (NSAIDs) within 1 month prior to qualification/baseline or anticipated use within the 12-month study period in the study eye 24. Use of warfarin, heparin, enoxaparin, or similar anticoagulants within 2 weeks prior to randomization or anticipated use at any time during the study 25. BCVA score < 34 letters (approximately 20/200 Snellen equivalent) in the nonstudy eye using the ETDRS method at qualification/baseline 26. Known allergy or hypersensitivity to the study medication or its components 27. Known allergy or contraindication to the use of fluorescein or povidone iodine 28. Female patients who are pregnant, nursing, or planning a pregnancy, or who are of childbearing potential and not using a reliable means of contraception 29. Current enrollment in an investigational drug or device study or participation in such a study within the 30 days prior to qualification/baseline
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E.5 End points |
E.5.1 | Primary end point(s) |
Best Corrected Visual Acuity (BCVA) is the primary efficacy parameter and the BCVA will be measured using the ETDRS method at each study visit (at Days 1 and 7 following the initial treatment or of open-label extension, BCVA will be considered as safety parameter). The primary efficacy variable is the proportion of patients with a BCVA improvement of 15 or more letters from baseline in the study eye at initial treatment Day 180.
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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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
sham controlled and open label on last 6 months |
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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.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 | 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 | |
E.8.9.1 | In the Member State concerned months | 27 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 45 |