Clinical trial NCT01505088: Safety and Efficacy Study of Iontophoretic Dexamethasone Phosphate Ophthalmic Solution to Treat Non-Infectious Anterior Segment Uveitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anterior Uveitis
Keywords: Iontophoresis
Non-Infectious Anterior Segment Uveitis
Ophthalmology
Lead sponsor: Eyegate Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2012-01-06
Enrollment: 193
Sex: ALL
Minimum age (years): 12
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients with with ACC count of zero at Day 14
timeFrame: At Day 14 (plus or minus two days) following the first study treatment
Secondary outcomes:
measure: Proportion of patients with ACC count of zero at Day 7
timeFrame: At Day 7 (plus or minus two days) following the first study treatment
measure: Proportion of patients with ACC count of zero at Day 28
timeFrame: At Day 28 (plus or minus two days) following the first study treatment
measure: Proportion of patients with ACC count of zero at Day 56
timeFrame: At Day 56 (plus or minus seven days) following the first study treatment
measure: Mean change from baseline in ACC count and score at Day 7
timeFrame: At Day 7 (plus or minus two days) following the first study treatment
measure: Mean change from baseline in ACC count and score at Day 14
timeFrame: At Day 14 (plus or minus two days) following the first study treatment
measure: Mean change from baseline in ACC count and score at Day 28
timeFrame: At Day 28 (plus or minus two days) following the first study treatment
measure: Mean change from baseline in ACC count and score at Day 56
timeFrame: At Day 56 (plus or minus seven days) following the first study treatment
measure: Proportion of subjects with ACC count and score reduction from baseline of one or more units at Day 7
timeFrame: At Day 7 (plus or minus two days) following the first study treatment
measure: Proportion of subjects with ACC count and score reduction from baseline of one or more units at Day 14
timeFrame: At Day 14 (plus or minus two days) following the first study treatment
measure: Proportion of subjects with ACC count and score reduction from baseline of one or more units at Day 28
timeFrame: At Day 28 (plus or minus two days) following the first study treatment
measure: Proportion of subjects with ACC count and score reduction from baseline of one or more units at Day 56
timeFrame: At Day 56 (plus or minus seven days) following the first study treatment
measure: Time to anterior chamber cell count and score of zero
timeFrame: Up to 56 days (plus or minus seven days) following the first study treatment
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Department of Ophthalmology at University of Alabama at Birmingham
state: Alabama
city: Chandler
country: United States
facility: Arizona Eye Center
state: Arizona
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Beverly Hills
country: United States
facility: Retina-Vitreous Associates Medical Group
state: California
city: Los Angeles
country: United States
facility: Doheny Eye Medical Group
state: California
city: Santa Ana
country: United States
facility: Orange County Retina Medical Group
state: California
city: Golden
country: United States
facility: Colorado Retina Associates
state: Colorado
city: Littleton
country: United States
facility: Corneal Consultants of Colorado
state: Colorado
city: Bridgeport
country: United States
facility: Connecticut Retina Consultants, LLC
state: Connecticut
city: Hamden
country: United States
facility: Eye Center of Southern Connecticut
state: Connecticut
city: New Haven
country: United States
facility: Yale Eye Center
state: Connecticut
city: Bradenton
country: United States
facility: The Eye Associates of Manatee, LLP
state: Florida
city: Jacksonville
country: United States
facility: Levenson Eye Associates
state: Florida
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Tamarac
country: United States
facility: Logan Ophthalmic Research
state: Florida
city: Atlanta
country: United States
facility: Emory Eye Center
state: Georgia
city: Fort Oglethorpe
country: United States
facility: Advanced Eye Care
state: Georgia
city: Chicago
country: United States
facility: Illinois Retina Associates
state: Illinois
city: Indianapolis
country: United States
facility: Raj K. Maturi, M.D. PC
state: Indiana
city: Ellsworth
country: United States
facility: Ellsworth Uveitis and Retina Care
state: Maine
city: Baltimore
country: United States
facility: Wilmer Eye Institute
state: Maryland
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Cambridge
country: United States
facility: Massachusetts Eye Research and Surgery Institution
state: Massachusetts
city: Chesterfield
country: United States
facility: Lifelong Vision Foundation
state: Missouri
city: Kansas City
country: United States
facility: Tauber Eye Center
state: Missouri
city: Washington
country: United States
facility: Comprehensive Eye Care Ltd.
state: Missouri
city: Palisades Park
country: United States
facility: Metropolitan Eye Research and Surgery Institute
state: New Jersey
city: New York
country: United States
facility: The New York Eye and Ear Infirmary
state: New York
city: Matthews
country: United States
facility: Charlotte Eye Ear Nose and Throat Associates
state: North Carolina
city: Portland
country: United States
facility: Casey Eye Institute
state: Oregon
city: Philadelphia
country: United States
facility: Scheie Eye Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: Mid-Atlantic Retina
state: Pennsylvania
city: Memphis
country: United States
facility: Southern College of Optometry
state: Tennessee
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: Houston
country: United States
facility: Houston Eye Associates
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: Norfolk
country: United States
facility: Virginia Eye Consultants
state: Virginia
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
Study officials:
affiliation: Virginia Eye Consultants
name: John D. Sheppard, M.D.
role: PRINCIPAL_INVESTIGATOR
References: