Safety and Effectiveness Investigation for Dry, Non-Exudative Age Related Macular Degeneration (AMD) Using Rheopheresis

Safety and Effectiveness, in a Multi-Center, Randomized, Sham Controlled Investigation for Dry, Non-Exudative Age Related Macular Degeneration (AMD)Using Rheopheresis

SUMMARY

Age-related macular degeneration (AMD) is the leading cause of late onset visual impairment and legal blindness in people 65 years of age or older in the United States. It is a heterogeneous clinical entity in which retinal degeneration occurs predominantly in the macula in the context of aging and leads to impairment primarily of central visual acuity. The degenerative retinal eye disease occurs in two forms - a non-exudative "dry" form and an exudative "wet" form which in an individual patient may also represent stages of the disease. Non-exudative AMD accounts for 80-90% of AMD cases and it involves a constellation of clinical features that can include drusen, pigment clumping and/or retinal pigment epithelium (RPE) dropout, and geographic atrophy. Because of the overwhelming numbers of "dry" AMD subjects, the cumulative impact of this vision loss is significant.

There is no effective therapy for maintaining or improving vision associated with dry AMD. The only therapy for persons with dry AMD is an oral supplement containing high doses of antioxidants and zinc, which was tested by the National Eye Institute in a large, multi-center, double-masked, sham-controlled clinical trial1. This antioxidant therapy was shown to modestly retard the progression of dry AMD from an intermediate stage to the advanced stages and confirmed the benefit of antioxidant therapy in this disease. There is currently no FDA-approved therapy for the treatment of subjects with dry AMD.

Recently, the MIRA-1 modified per protocol population showed the effectiveness of Rheopheresis which is an application of selective therapeutic apheresis, namely double filtration plasmapheresis (DFPP) using a specifically designed filter for plasma filtration in subjects with non-exudative AMD. At one year the study reported with statistical significance (1) approximately a one line vision improvement in the Rheopheresis group versus no change in the Sham group and (2) 28% of subjects randomized to the active treatment gaining at least one line vision versus only 9% of subjects randomized to the sham treatment.

With a total of 300 subjects with dry AMD and visual acuity of 20/40-20/100 inclusive, the current investigation plans to prove the effectiveness of the Rheopheresis treatment on a larger scale. Each subject will receive a series of 8 treatments (either active treatment or sham treatment in a 2:1 ratio) for a period of approximately 2.5 months. In addition, a post-treatment ophthalmic evaluation will be performed 2 weeks after the 8th treatment (approximately 3 months after the baseline visit) and at the 6, 9 and 12 month visits. Comparing the one-year proportions of at least a 10-letter gain in ETDRS LogMar BCVA from baseline, the current investigation will show the effectiveness of Rheopheresis treatment (compared to sham treatment) for treating dry AMD subjects. Other secondary effectiveness endpoints, including mean changes and proportions of BCVA better than 20/40 at one year, will be analyzed to support the main investigation.

Inclusion Criteria:

• Study eye must have a diagnosis of non-exudative, "Dry", AMD with equivalent drusen surface area of approximately 31,000 µm2 [e.g. at least 10 soft, semi-soft intermediate size ≥63µm or at least 3 drusen size ≥125 µm within 3,000 µm of the fovea documented on macular exam, retinal angiography and fundus photographs as determined by the reading center. ETDRS BCVA of 20/40 - 20/100 inclusive

Exclusion Criteria:

• Either eye with previous or active sub-retinal neovascularization (SRNV) or choroidal neovascularization (CNV)
• Pigment epithelial detachment (PED) within 500 µm of the fovea
• Either eye with a diagnosis of exudative (wet) AMD
• Subjects having undergone cataract surgery less than 3 months prior to enrollment without an open posterior capsule
• Uncontrolled hypertension and/or diabetes
• Subjects with prolonged PT/PTT (unless the subject is taking warfarin), hematocrit <35%, evidence of active bleeding, platelet count <100,000/ml