Safety and Efficacy Study of Iontophoretic Dexamethasone Phosphate Ophthalmic Solution to Treat Non-Infectious Anterior Segment Uveitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of ocular iontophoresis with dexamethasone phosphate ophthalmic solution EGP-437 using the EyeGate® II Drug Delivery System (EGDS) compared to prednisolone acetate ophthalmic suspension (1%) in patients with non-infectious anterior segment uveitis.

Detailed Description
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Anterior uveitis is a disorder of the eye associated with intraocular inflammation of the anterior portion of the uvea, particularly the iris and/or ciliary body. It is distinct from other iterations of uveitis such as posterior, diffuse and intermediate uveitis although it is the most common form of uveitis and accounts for approximately 75% of cases. In a Phase 1/2 study (EGP-437-001), the delivery of EGP-437 (40 mg/mL dexamethasone phosphate solution) at four different iontophoresis dose levels was studied in 40 subjects with non-infectious anterior segment uveitis. The study demonstrated that a single EGP-437 treatment: lowered anterior chamber cell (ACC) scores in the majority of patients without requiring additional treatment; produced low short-term systemic exposure to dexamethasone and dexamethasone phosphate; and produced the most beneficial effects in the 1.6 and 4.8 mA-min dose groups; and caused mainly minor AEs and no non-ocular systemic corticosteroid mediated effects were observed. The Phase 3 study is intended to confirm and extend the results from the Phase 2 study. The study is designed to assess the safety and efficacy Ocular Iontophoresis with EGP-437 4.0 mA-min at 1.5 mA and accompanying placebo eyedrops in comparison to Ocular Iontophoresis with sodium citrate buffer solution 4.0 mA-min at 1.5 mA and accompanying prednisolone acetate (1%) eyedrops for the treatment of non-infectious anterior segment uveitis.

Official Title
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A Prospective, Multi-Center, Randomized, Double-Masked, Positive-Controlled Phase 3 Clinical Trial Designed to Evaluate the Safety and Efficacy of Iontophoretic Dexamethasone Phosphate Ophthalmic Solution Compared to Prednisolone Acetate Ophthalmic Suspension (1%) in Patients With Non-Infectious Anterior Segment Uveitis

Conditions
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Anterior Uveitis

Intervention / Treatment
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* Drug: 40 mg/mL Dexamethasone phosphate ophthalmic solution
* Drug: Prednisolone Acetate (1%) Eyedrops
* Drug: 100 mM sodium citrate buffer solution
* Drug: Placebo Eyedrops


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age 12 to 85 years with a diagnosis of non-infectious anterior segment uveitis defined as an anterior chamber cell count of ≥ 11 cells Receive, understand, and sign a copy of the written informed consent form Be able to return for all study visits and willing to comply with all study-related instructions Exclusion Criteria: Have uveitis of infectious etiology Have active intermediate or posterior uveitis Known positive HLA-B27 with a severe (4+) fibrinoid reaction Have previous anterior segment uveitis episode in the study eye ≤ 4 weeks prior to baseline visit Have used topical corticosteroid treatment in the study eye ≤ 48 hours prior to baseline visit Have used oral corticosteroid within the past 14 days prior to baseline Have received intravitreal or sub-Tenon corticosteroid treatment in the study eye within the past 6 months prior to baseline visit Currently using prescribed nonsteroidal anti-inflammatory agents (i.e., use of over-the-counter dosages is allowable) or prescribed immunosuppressive agents, unless the dose has been stable for the last six weeks and no change in dosing is anticipated for the duration of the study Have IOP ≥ 25 mmHg at baseline, a history of glaucoma, or require ocular anti-hypertensive medications in the study eye Be known steroid intraocular pressure responders in either eye Have open wounds/skin disease on the forehead area where the iontophoresis return electrode will be applied Have severe lesions of the eyelids or the ocular surface impeding the application of the iontophoresis applicator Have known allergy to dexamethasone or dexamethasone phosphate or any medication to be used in this study Have history or diagnosis of ocular herpes, corneal lesion of suspected herpetic origin, or Behçet's disease Have monocular or BCVA worse than 20/80 in the fellow eye Have optic neuritis of any origin Have clinically suspected or confirmed central nervous system or ocular lymphoma Planning to undergo elective ocular surgery during the study Have active hyphema, pars planitis, choroiditis, clinically significant macular edema, toxoplasmosis scar, or vitreous hemorrhage Have severe/serious ocular pathology or medical condition which may preclude study completion Have pacemaker and/or any other electrical sensitive support system Be pregnant or lactating female, or female of childbearing age and using inadequate birth control method Have participated in another investigational device or drug study within 30 days of baseline visit Have significant Fuch's Corneal Dystrophy

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 85 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iontophoretic Dexamethasone Phosphate Ophthalmic Solution<br>Dexamethasone phosphate (40 mg/mL) solution delivered by iontophoresis treatment consisting of 4.0 mA-min at 1.5 mA on Day 0 and Day 7 with accompanying placebo eyedrops (saline solution) for up to 28 days. | Drug: 40 mg/mL Dexamethasone phosphate ophthalmic solution<br>* Transscleral iontophoresis delivery of EGP-437 (dexamethasone phosphate formulated for ocular iontophoresis)<br>Drug: Placebo Eyedrops<br>* Placebo Eyedrops<br>* Other names: Saline/ Benzalkonium Chloride (BAK) Ophthalmic Solution;|
| Active Comparator: Prednisolone Acetate Ophthalmic Suspension (1%)<br>Placebo (100 mM sodium citrate buffer solution) iontophoresis treatment consisting of 4.0 mA-min at 1.5 mA on Day 0 and Day 7 with accompanying prednisolone acetate ophthalmic suspension (1%) (positive control) eyedrops for up to 28 days. | Drug: Prednisolone Acetate (1%) Eyedrops<br>* Prednisolone acetate (1%) eyedrops<br>Drug: 100 mM sodium citrate buffer solution<br>* Transscleral iontophoresis delivery of 100 mM Sodium citrate buffer solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with with ACC count of zero at Day 14 | Proportion of patients with ACC count of zero at Day 14 | At Day 14 (plus or minus two days) following the first study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with ACC count of zero at Day 7 | Proportion of patients with ACC count of zero at Day 7 | At Day 7 (plus or minus two days) following the first study treatment | 
| Proportion of patients with ACC count of zero at Day 28 | Proportion of patients with ACC count of zero at Day 28 | At Day 28 (plus or minus two days) following the first study treatment | 
| Proportion of patients with ACC count of zero at Day 56 | The proportion of patients with ACC count of zero at Day 56 | At Day 56 (plus or minus seven days) following the first study treatment | 
| Mean change from baseline in ACC count and score at Day 7 | Mean change from baseline in ACC count and score at Day 7 | At Day 7 (plus or minus two days) following the first study treatment | 
| Mean change from baseline in ACC count and score at Day 14 | Mean change from baseline in ACC count and score at Day 14 | At Day 14 (plus or minus two days) following the first study treatment | 
| Mean change from baseline in ACC count and score at Day 28 | Mean change from baseline in ACC count and score at Day 28 | At Day 28 (plus or minus two days) following the first study treatment | 
| Mean change from baseline in ACC count and score at Day 56 | Mean change from baseline in ACC count and score at Day 56 | At Day 56 (plus or minus seven days) following the first study treatment | 
| Proportion of subjects with ACC count and score reduction from baseline of one or more units at Day 7 | Proportion of subjects with ACC count and score reduction from baseline of one or more units at Day 7 | At Day 7 (plus or minus two days) following the first study treatment | 
| Proportion of subjects with ACC count and score reduction from baseline of one or more units at Day 14 | Proportion of subjects with ACC count and score reduction from baseline of one or more units at Day 14 | At Day 14 (plus or minus two days) following the first study treatment | 
| Proportion of subjects with ACC count and score reduction from baseline of one or more units at Day 28 | Proportion of subjects with ACC count and score reduction from baseline of one or more units at Day 28 | At Day 28 (plus or minus two days) following the first study treatment | 
| Proportion of subjects with ACC count and score reduction from baseline of one or more units at Day 56 | Proportion of subjects with ACC count and score reduction from baseline of one or more units at Day 56 | At Day 56 (plus or minus seven days) following the first study treatment | 
| Time to anterior chamber cell count and score of zero | Time to anterior chamber cell count and score of zero | Up to 56 days (plus or minus seven days) following the first study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iontophoresis, Non-Infectious Anterior Segment Uveitis, Ophthalmology