The Wilmer Ophthalmological Institute at Johns Hopkins University School of Medicine in Baltimore is conducting a pilot study to assess the safety and efficacy of a fluocinolone acetonide ocular delivery system (Iluvien/Medidur FA, Alimera Sciences, Alpharetta, GA) in conjunction with intravitreally injected ranibizumab (Lucentis, Genen-tech) in patients with exudative age-related macular degeneration (AMD). The MAP (Medidur for AMD Pilot) Study is being conducted under the leadership of Peter Campochiaro, MD, the Eccles Professor of Ophthalmology and Neuroscience at the Johns Hopkins University School of Medicine. Alimera Sciences intends to market Medidur FA, as it is referred to in the trial, under the trade name Iluvien, if approved by the US Food and Drug Administration.

STUDY RATIONALE
Treatment of exudative AMD has been significantly improved with the advent of ranibizumab, which provides improvement, in addition to stabilization, of vision in some patients with AMD. Frequent injections of ranibizumab, however, may be required to maintain the beneficial effect on vision. A combination approach to therapy, with the antiangiogenic properties of a vascular endothelial growth factor (VEGF) antagonist (ranibizumab) and of an antiinflammatory agent (fluocinolone acetonide), may have the potential to reduce the frequency of ranibizumab injections.

METHOD OF DRUG DELIVERY
Iluvien, a very small, injectable intravitreal insert, is currently being investigated as an approach to deliver a very low dose of fluocinolone acetonide, a corticosteroid, to the retina for up to 3 years as a treatment for diabetic macular edema (DME) in the FAME (Fluocinolone Acetonide for Diabetic Macular Edema) phase 3 clinical trial. Using a proprietary 25-gauge inserter system, the retina specialist inserts Iluvien into the vitreous through a minimally invasive procedure in an outpatient office setting.

The use of the glucocorticoids, such as triamicinolone acetonide, as an adjunct treatment for neovascular AMD, has been reported to enhance the efficacy of photodynamic therapy with verteporfin for injection (Visudyne, Novartis). Therefore, it is hypothesized that the sustained-release fluocinolone acetonide, when employed in conjunction with intravitreal injections of ranibizumab, will allow maintenance of the gain in vision exerted by ranibizumab but with fewer injections. The MAP Study, a pilot phase 2b study, is being conducted to evaluate this hypothesis. Primary analysis will be performed at 6 months, but bioactivity and safety assessments will continue through 36 months.

The MAP Study will compare the safety and bioactivity of two doses of Iluvien (patients will be randomized to either 0.2 or 0.5 µg/day), in conjunction with ranibizumab (as needed).

TRIAL DESIGN
The MAP Study will enroll up to 30 patients who meet inclusion/exclusion criteria.

Patients included will be 50 years of age or older, will have been treated with intraocular injections of ranibizumab for at least 6 months, and will and have reached a plateau, defined as two consecutive visits (4 to 6 weeks apart) with no improvement in visual acuity (worse or within one line better) or center subfield thickening (worse or within 30 µm better). Best corrected visual acuity must be 20/320 or better in the study eye.

In addition to typical exclusion criteria, patients with glaucoma, with intraocular pressure (IOP) of ≥21 mm Hg, or on IOP-lowering medication(s), are excluded because of the potential IOP-raising effect of steroids. Eligible patients will receive an intraocular injection of ranibizumab and an Iluvien insert (0.2 or 0.5 µg/day). Patients will return for monthly evaluations and will receive an injection of ranibizumab unless there is no subretinal or intraretinal fluid in the macula as demonstrated by optical coherence tomography (OCT). Patients will be masked with regard to treatment group.

OUTCOMES ANALYSIS
The primary outcome measure is the mean change from baseline in visual acuity at 6 months. Secondary outcome measures include the mean change from baseline in central subfield thickening at 6 months, the change from baseline in the percentage of patients with visual acuity of 20/40 or better, the mean number of injections of ranibizumab over the 6-month study period compared with the 6 months prior to study entry, the percentage of patients with complete elimination of intraretinal and subretinal fluid by OCT, and the percentage of patients with complete elimination of fluorescein leakage at 6 months compared with baseline. The two dose groups will be compared. The study, however, is not powered for statistical testing.

In conclusion, it is the hope of the MAP Study investigators that the results will provide additional insights into the pathogenesis of choroidal neovascularization and the management of exudative AMD.

Quan Dong Nguyen, MD, MSc, is Associate Professor of Ophthalmology for Diseases of the Retina and Vitreous, and Uveitis at the Wilmer Ophthalmological Institute, the Johns Hopkins University School of Medicine in Baltimore. The Johns Hopkins University, the employer of Dr. Nguyen, receives research funding from Genentech, Inc., and Alimera Sciences, Inc. Dr. Nguyen can be reached at +1 410 502 9821; or via e-mail at qnguyen4@jhmi.edu.

The views expressed by Dr. Nguyen do not imply endorsement by the Johns Hopkins University or the Johns Hopkins Medical Institutions.