Ozurdex Monotherapy Trial

Study Overview
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Brief Summary
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This study will investigate the efficacy and safety of OZURDEX® (dexamethasone intravitreal implants; DEX, Allergan, Inc. Irvine, CA) as monotherapy for the treatment of non-infectious intermediate-, posterior- or panuveitis. This is a prospective randomized controlled clinical trial taking place at the University of Ottawa Eye Institute, Ottawa, Ontario, Canada, and other possible centers in Canada. Consecutive consenting subjects who meet inclusion/exclusion criteria will be selected to participate in this study. The subjects must have either non-infectious intermediate, posterior, or panuveitis. The subjects will be randomly chosen to be part of one of two groups; one group will receive DEX as monotherapy and the other group will receive oral prednisone. Approximately 84 eyes (42 per arm) will take part in study. The primary outcome will measure the proportion of eyes with a vitreous haze score of 0 six months post initial treatment. Secondary measures will include best corrected visual acuity (BCVA), central retinal thickness (CRT) measured by spectral-domain optical coherence tomography (SD-OCT), time to vitreous haze resolution and time to failure defined at number of months with DEX implant until an adjunct therapy is indicated. Baseline measurements will be recorded within 1 month prior to treatment in both groups, with follow up measurements collected at 0, 1, 2, 4, 6 and 12 months post-operatively.

Official Title
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Ozurdex as Monotherapy for Treatment of Non-infectious Intermediate, Posterior, or Panuveitis

Conditions
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Uveitis, Posterior, Uveitis, Intermediate, Panuveitis

Intervention / Treatment
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* Drug: Ozurdex 0.7mg Ophthalmic Implant
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Diagnosis of non-infectious intermediate, posterior, or panuveitis in at least one eye Active uveitic disease at Screening/Baseline defined by the presence of at least 1 of the following parameters: 1) Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion 2) ≥ 1+ vitreous haze (NEI/SUN criteria) Exclusion Criteria: Presence of isolated anterior uveitis Evidence of macular edema due to diabetes, retinal vein occlusion or any other ocular conditions Confirmed or suspected active ocular disease or infections Intraocular surgery in the past 6 months History of glaucoma Intraocular pressure (IOP) of >21 mmHg at Screening/Baseline or confirmed normal-tension glaucoma Intravitreal or periocular injection within 6 months prior to screening. Unable to tolerate systemic corticosteroids Prior topical corticosteroid within 1 month of screening Prior non-steroidal anti-inflammatory, systemic steroids, or immunomodulatory therapy (e.g. methotrexate) within 1 month of screening For women: pregnant or breast feeding, or planning to become pregnant while enrolled in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravitreal Dexamethasone Implant Group<br>Subjects randomized to the experimental group will receive a 0.7mg intravitreal dexamethasone (DEX) implant which will be injected in the vitreous cavity as one of the treatments of interest in this study. | Drug: Ozurdex 0.7mg Ophthalmic Implant<br>* A 0.7mg intravitreal dexamethasone implant will be used for the treatment of posterior, intermediate and panuveitis for minimum of 6 months.<br>|
| Active Comparator: Prednisone Taper Group<br>Subjects randomized to the comparator group will receive oral prednisone. The initial dose is expected to range between 40 to 60mg of oral prednisone per day, with gradual tapering to the lowest dose that controls inflammation and eventually transitioning to a maintenance dose. Maintenance dose will be gradually lowered as per standard of care if remission is achieved for 6 to 12 months. | Drug: Prednisone<br>* The comparator will be a prednisone taper which is currently the standard care for the uveitis types of focus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with Vitreous Haze score of 0 at 6 months | This score (using NEI/SUN criteria) is used to grade intraocular inflammation based on vitreous cells and protein exudation. A lower score is indicative of less inflammation which is the goal when using either Ozurdex implant or a oral prednisone. | Measurements obtained at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Corrected Visual Acuity at various time points | This score will be used to determine the functional outcome (visual acuity) with the treatments. | Measurements obtained at: 1 month, 2 months, 4 months, 6 months, 12 months | 
| Proportion of patients with vitreous haze improvement by 1, and 2 units from baseline to various time points | This score will be used to look at the degree of changes in the inflammation. | Measurements obtained at: 1 month, 2 months, 4 months, 6 months, 12 months | 
| Time to vitreous haze score of 0 from baseline to various time points | This will be used to assess if there are differences in time to achieving lowest possible inflammation amongst groups. | Measurements obtained at: 1 month, 2 months, 4 months, 6 months, 12 months | 
| Anterior chamber cells/flare from baseline to various time points | Using SUN grading criteria, the proportion of patients with cells grade 0, 0.5+, 1+, 2+, 3+, 4+ and flare grade of 0, 1+, 2+, 3+, 4+ will be determined at Month 6. | Measurements obtained at: 1 month, 2 months, 4 months, 6 months, 12 months | 
| Change in central average thickness (µm) from baseline to various time points | This score will be used to assess anatomical changes (e.g. cystoid macular edema) with treatment | Measurements obtained at: 1 month, 2 months, 4 months, 6 months, 12 months | 
| Change in central average volume (in mm3) from baseline to various time points | This score will be used to assess anatomical changes (e.g. cystoid macular edema) with treatment | Measurements obtained at: 1 month, 2 months, 4 months, 6 months, 12 months | 
| Change in National Eye Institute Visual Function Questionnaire 25 Score | This will be used to determine impact of disease on the subject's quality of life. The worst possible score is 0 while best is 100. The higher the score, the higher the subjective visual function. | Baseline and 12mo | 
| Incidence of complications | Measure complication of treatment including but not limited to cataracts formation, ocular hypertension, vitreous hemorrhage, and endophthalmitis. | Anywhere between baseline to 12 months | 
| Percentage of patients with Vitreous Haze score of 0 at various time points | This score (using NEI/SUN criteria) is used to grade intraocular inflammation based on vitreous cells and protein exudation. A lower score is indicative of less inflammation which is the goal when using either Ozurdex implant or a oral prednisone. | Measurements obtained at: 1 month, 2 months, 4 months, 6 months (primary outcome), 12 months |