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

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

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.

Study Overview

• Status: Completed
• Conditions: Anterior Uveitis
• Intervention / Treatment: Drug: 40 mg/mL Dexamethasone phosphate ophthalmic solution; Drug: Placebo Eyedrops; Drug: Prednisolone Acetate (1%) Eyedrops; Drug: 100 mM sodium citrate buffer solution

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.

• Study Type: Interventional
• Enrollment (Actual): 193
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Department of Ophthalmology at University of Alabama at Birmingham
  • Arizona
    • Chandler, Arizona, United States, 85225
      • Arizona Eye Center
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants
  • California
    • Beverly Hills, California, United States, 90211
      • Retina-Vitreous Associates Medical Group
    • Los Angeles, California, United States, 90033
      • Doheny Eye Medical Group
    • Santa Ana, California, United States, 92705
      • Orange County Retina Medical Group
  • Colorado
    • Golden, Colorado, United States, 80401
      • Colorado Retina Associates
    • Littleton, Colorado, United States, 80120
      • Corneal Consultants of Colorado
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Connecticut Retina Consultants, LLC
    • Hamden, Connecticut, United States, 06518
      • Eye Center of Southern Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Eye Center
  • Florida
    • Bradenton, Florida, United States, 34209
      • The Eye Associates of Manatee, LLP
    • Jacksonville, Florida, United States, 32204
      • Levenson Eye Associates
    • Miami, Florida, United States, 33136
      • Bascom Palmer Eye Institute
    • Tamarac, Florida, United States, 33321
      • Logan Ophthalmic Research
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Eye Center
    • Fort Oglethorpe, Georgia, United States, 30742
      • Advanced Eye Care
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Illinois Retina Associates
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Raj K. Maturi, M.D. PC
  • Maine
    • Ellsworth, Maine, United States, 04605
      • Ellsworth Uveitis and Retina Care
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Wilmer Eye Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts Eye and Ear Infirmary
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
    • Cambridge, Massachusetts, United States, 02142
      • Massachusetts Eye Research and Surgery Institution
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Lifelong Vision Foundation
    • Kansas City, Missouri, United States, 64111
      • Tauber Eye Center
    • Washington, Missouri, United States, 63090
      • Comprehensive Eye Care Ltd.
  • New Jersey
    • Palisades Park, New Jersey, United States, 07650
      • Metropolitan Eye Research and Surgery Institute
  • New York
    • New York, New York, United States, 10003
      • The New York Eye and Ear Infirmary
  • North Carolina
    • Matthews, North Carolina, United States, 28105
      • Charlotte Eye Ear Nose and Throat Associates
  • Oregon
    • Portland, Oregon, United States, 97239
      • Casey Eye Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid-Atlantic Retina
    • Philadelphia, Pennsylvania, United States, 19104
      • Scheie Eye Institute
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Southern College of Optometry
  • Texas
    • Austin, Texas, United States, 78705
      • Austin Retina Associates
    • Houston, Texas, United States, 77025
      • Houston Eye Associates
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthalmology Associates
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Eye Consultants
  • Washington
    • Spokane, Washington, United States, 99204
      • Spokane Eye Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 83 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Iontophoretic Dexamethasone Phosphate Ophthalmic Solution; 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; Transscleral iontophoresis delivery of EGP-437 (dexamethasone phosphate formulated for ocular iontophoresis); Drug: Placebo Eyedrops; Placebo Eyedrops; Other Names: Saline/ Benzalkonium Chloride (BAK) Ophthalmic Solution
Active Comparator: Prednisolone Acetate Ophthalmic Suspension (1%); 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; Prednisolone acetate (1%) eyedrops; Drug: 100 mM sodium citrate buffer solution; Transscleral iontophoresis delivery of 100 mM Sodium citrate buffer solution

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eyegate Pharmaceuticals, Inc.
• Investigators: Principal Investigator: John D. Sheppard, M.D., Virginia Eye Consultants

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: January 4, 2012
• First Submitted That Met QC Criteria: January 5, 2012
• First Posted (Estimate): January 6, 2012

Study Record Updates

• Last Update Posted (Estimate): March 29, 2013
• Last Update Submitted That Met QC Criteria: March 28, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Ophthalmology; Iontophoresis; Non-Infectious Anterior Segment Uveitis
• Additional Relevant MeSH Terms: Eye Diseases; Panuveitis; Uveal Diseases; Iris Diseases; Uveitis; Uveitis, Anterior; Iridocyclitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Anticoagulants; Chelating Agents; Sequestering Agents; Calcium Chelating Agents; Dexamethasone; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Ophthalmic Solutions; Pharmaceutical Solutions; Dexamethasone 21-phosphate; Citric Acid; Sodium Citrate; Benzalkonium Compounds
• Other Study ID Numbers: EGP-437-004