| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Non-infectious ocular inflammation of the posterior segment in intermediate or posterior uveitis |
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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 Sham DEX PS DDS Applicator System (needle-less applicator) in the treatment of non-infectious ocular inflammation of the posterior segment in patients with intermediate or posterior uveitis |
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| E.2.2 | Secondary objectives of the trial |
| To evaluate the 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 the treatment of non-infectious ocular inflammation of the posterior segment in patients with intermediate or posterior uveitis |
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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. Diagnosis of intermediate or posterior uveitis in at least one eye based on the standardization of uveitis nomenclature for reporting clinical data workshop. (SUN Working Group classification report published AJO 2005; 140:509-516). For diagnosis of intermediate uveitis (e.g. pars planitis, posterior cyclitis, hyalitis), the vitreous must be the primary site of inflammation. The presence of peripheral vascular sheathing and macular edema is acceptable as long as the vitreous remains the main site of inflammation. For diagnosis of posterior uveitis, the retina or choroid must be the primary site of inflammation. Suspected masquerade syndromes should be ruled out by the investigator prior to patient entry into the study
3. Vitreous haze of at least +1.5 at both the screening and baseline visits in the study eye
4. Best-corrected ETDRS visual acuity score of 10 to 75 letters inclusive (Snellen equivalent approximately 20/640 – 20/32) at screening and baseline visits in the study eye
5. Media clarity other than vitreous haze, pupillary dilation, and patient cooperation sufficient for adequate visualization of the optic nerve in the study eye
6. Allowable treatments at screening, baseline, and treatment (Day 0) visits:
6.1. Topical corticosteroids and NSAIDs (e.g. ketorolac, diclofenac) if doses are stable for at least 2 weeks prior to screening and remain stable through treatment (Day 0)
6.2. Systemic immunosuppression (e.g., cyclosporine, methotrexate) if doses are stable for at least 3 months prior to screening and remain stable through treatment (Day 0)
6.3. Systemic corticosteroids if doses are ≤20 mg/day oral prednisone (or equivalent), are stable for at least 1 month prior to screening and remain stable through treatment (Day 0)
6.4. Topical cycloplegia (e.g. homatropine, atropine) at the investigator’s discretion
7. Female patients of childbearing potential must have a negative urine pregnancy test at the treatment (Day 0) visit
8. Written informed consent has been obtained
9. Written Authorization for Use and Release of Health and Research Study Information (US sites only) has been obtained
10. Written Data Protection Consent (European sites only) has been obtained
11. Written documentation has been obtained in accordance with state and country privacy requirements, where applicable
12. Ability to understand the informed consent and willingness to follow study instructions and likely to complete all required visits and procedures
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| E.4 | Principal exclusion criteria |
General exclusion criteria:
1. Female patients who are pregnant, nursing, or planning a pregnancy, or who are of childbearing potential and not using a reliable means of contraception
2. Uncontrolled systemic disease or known human immunodeficiency virus (HIV) infection
3. Participation in an investigational trial within 30 days of study entry
4. Use of warfarin/heparin/enoxaparin or similar anticoagulant agent ≤ 2 weeks prior to the treatment (Day 0) visit
5. Known allergy or sensitivity to the study medication(s), any component of the delivery vehicle, any corticosteroids or any diagnostic agents used during the study (e.g. fluorescein, dilation drops)
6. Anticipated need to initiate or change doses of current systemic immunosuppression or systemic corticosteroids during the first 8 weeks of the study
7. Any condition (including inability to read visual acuity charts or language barrier) that precludes patient’s ability to comply with study requirements including completion of the study
8. Patient has a condition or is in a situation that in the investigator's opinion may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient's participation in the study
Ocular exclusion criteria:
1. Previous enrollment in a DEX PS DDS clinical trial
2. IOP > 21 mm Hg at screening or baseline
3. History of clinically significant IOP elevation in response to corticosteroid treatment in either eye (defined as an increase of >10 mm Hg and an absolute IOP of ≥25 mm Hg without the use of anti-glaucoma medications) unless there is a functioning trabeculectomy or seton (with IOP <18 mm Hg at screening and baseline) and there is no significant visual field loss in the investigator’s opinion
4. History, diagnosis, or clinical findings of ocular hypertension or glaucoma (e.g. elevated IOP, optic nerve head change consistent with glaucoma, glaucomatous visual field loss) in the study eye unless there is a functioning trabeculectomy or seton (with IOP <18 mm Hg at screening and baseline) and there is no significant visual field loss in the investigator’s opinion. Patients with a history of episodic increases in IOP due to inflammation and not due to corticosteroids may be eligible if they meet all other IOP and glaucoma medication exclusions
5. Use of anti-glaucoma medications in the study eye within 4 weeks prior to the screening visit or any use between screening and treatment visits
6. History of central serous chorioretinopathy in either eye
7. Any active ocular infection (i.e. bacterial, viral, parasitic, or fungal) in either eye at screening, baseline, or treatment visits
8. Presence of active or inactive toxoplasmosis in either eye
9. Contraindication to pupil dilation in either eye
10. Any other ocular disease (e.g. choroidal neovascularization, media opacity) in the study eye that can interfere with the diagnosis or the assessment of disease progression
11. Periocular corticosteroid injections to the study eye ≤ 8 weeks prior to the treatment visit
12. History of any intravitreal drug injection to the study eye ≤ 26 weeks prior to the treatment visit
13. History of any intravitreal corticosteroid injection to the study eye unless all of the following criteria are met:
a. The only corticosteroid injected intravitreally was triamcinolone acetonide
b. The most recent dose was > 26 weeks prior to the treatment visit
c. All doses were ≤4 mg
14. Any previous use of RetisertTM (fluocinolone acetonide intravitreal implant) in the study eye
15. Intraocular surgery, including cataract surgery, and/or laser of any type in the study eye ≤ 90 days prior to the treatment visit
16. Aphakia or anterior chamber intraocular lens in the study eye (posterior chamber IOL is acceptable)
17. History of pars plana vitrectomy in the study eye
18. History of herpetic infection in the study eye or adnexa
19. Presence of visible scleral thinning or ectasia in the study eye at screening, baseline, or treatment visits
20. Best-corrected ETDRS visual acuity score < 34 letters (approximately 20/200 on the Snellen scale) in the non-study eye using the ETDRS method at the screening or baseline visit
21. Uveitis expected to be unresponsive to corticosteroids or uveitis unresponsive to prior corticosteroids
22. Hypotony (IOP < 5 mm Hg or clinical signs such as choroidals, choroidal or corneal folds) or pre-phthisis (e.g. scleral thickening on ultrasonography, decreasing globe size)
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy variable is vitreous haze. The ophthalmologist will grade vitreous haze by viewing the optic disc and posterior retina using an indirect ophthalmoscope set to large beam and mid power illumination with a 20-diopter lens. Low ambient lighting and the same indirect ophthalmoscope should be used whenever possible. The view will be compared against a photographic standardized scale according to the chart provided by Allergan. The scale is based on the following unit scale categorized as follows:
0 = No inflammation
+0.5 = Trace inflammation (slight blurring of the optic disc margins and/ or loss of the NFL reflex)
+1 = Mild blurring of retinal vessels and optic nerve
+1.5 = Optic nerve head and posterior retina view obscuration greater than +1, but less than +2
+2 = Moderate blurring of optic nerve head
+3 = Marked blurring of optic nerve head
+4 = Optic nerve head not visible
There is no primary safety endpoint for the study |
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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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 |
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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 | 25 |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
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