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

Anterior Uveitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01505088
• Other study ID #: EGP-437-004
• Status: Completed
• Phase: Phase 3
• First received: January 4, 2012
• Last updated: March 28, 2013
• Start date: December 2011
• Est. completion date: March 2013

Study information

• Verified date: March 2013
• Source: Eyegate Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 193
• Est. completion date: March 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anterior Uveitis
• Iridocyclitis
• Iritis
• Uveitis
• Uveitis, Anterior

Intervention

Drug:
• 40 mg/mL Dexamethasone phosphate ophthalmic solution
Transscleral iontophoresis delivery of EGP-437 (dexamethasone phosphate formulated for ocular iontophoresis)
• Prednisolone Acetate (1%) Eyedrops
Prednisolone acetate (1%) eyedrops
• 100 mM sodium citrate buffer solution
Transscleral iontophoresis delivery of 100 mM Sodium citrate buffer solution
• Placebo Eyedrops
Placebo Eyedrops

Locations

Country	Name	City	State
United States	Emory Eye Center	Atlanta	Georgia
United States	Austin Retina Associates	Austin	Texas
United States	Wilmer Eye Institute	Baltimore	Maryland
United States	Retina-Vitreous Associates Medical Group	Beverly Hills	California
United States	Department of Ophthalmology at University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	The Eye Associates of Manatee, LLP	Bradenton	Florida
United States	Connecticut Retina Consultants, LLC	Bridgeport	Connecticut
United States	Massachusetts Eye Research and Surgery Institution	Cambridge	Massachusetts
United States	Arizona Eye Center	Chandler	Arizona
United States	Lifelong Vision Foundation	Chesterfield	Missouri
United States	Illinois Retina Associates	Chicago	Illinois
United States	Ellsworth Uveitis and Retina Care	Ellsworth	Maine
United States	Advanced Eye Care	Fort Oglethorpe	Georgia
United States	Colorado Retina Associates	Golden	Colorado
United States	Eye Center of Southern Connecticut	Hamden	Connecticut
United States	Houston Eye Associates	Houston	Texas
United States	Raj K. Maturi, M.D. PC	Indianapolis	Indiana
United States	Levenson Eye Associates	Jacksonville	Florida
United States	Tauber Eye Center	Kansas City	Missouri
United States	Corneal Consultants of Colorado	Littleton	Colorado
United States	Doheny Eye Medical Group	Los Angeles	California
United States	Charlotte Eye Ear Nose and Throat Associates	Matthews	North Carolina
United States	Southern College of Optometry	Memphis	Tennessee
United States	Bascom Palmer Eye Institute	Miami	Florida
United States	Yale Eye Center	New Haven	Connecticut
United States	The New York Eye and Ear Infirmary	New York	New York
United States	Virginia Eye Consultants	Norfolk	Virginia
United States	Metropolitan Eye Research and Surgery Institute	Palisades Park	New Jersey
United States	Mid-Atlantic Retina	Philadelphia	Pennsylvania
United States	Scheie Eye Institute	Philadelphia	Pennsylvania
United States	Associated Retina Consultants	Phoenix	Arizona
United States	Casey Eye Institute	Portland	Oregon
United States	Medical Center Ophthalmology Associates	San Antonio	Texas
United States	Orange County Retina Medical Group	Santa Ana	California
United States	Spokane Eye Clinical Research	Spokane	Washington
United States	Logan Ophthalmic Research	Tamarac	Florida
United States	Comprehensive Eye Care Ltd.	Washington	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Eyegate Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes