Metformin for the Minimization of Geographic Atrophy Progression in Patients With AMD

This is a phase II, single-blind, randomized, evaluation of the safety and efficacy of
metformin use to decrease geographic atrophy (GA) progression in non-diabetic patients with
dry Age-related Macular Degeneration (AMD). Approximately 186 study subjects throughout four
separate study sites will be randomized in a 1:1 ratio to the treatment group and the
observation group. The treatment group will be assigned to the study intervention (oral
Metformin) for 18 months while the observation group will receive no intervention for 18
months, instead continuing with standard of care ophthalmic exams and close monitoring of
their disease. There will be one additional follow up visit at 24 months. Throughout the 24
month study period, the progression of subjects' GA or drusen growth will be measured via
ocular imaging taken at standard of care follow-up examinations, including fundus
autofluorescence imaging, optical coherence tomography (OCT), and fundus photography.

Inclusion Criteria:

- Subject must be >/= 55 years of age

- Subject must have evidence of advanced dry AMD, defined by the characteristic presence
of drusen and/or pigmentary changes as well as geographic atrophy

- Subject must have clear ocular media and adequate pupillary dilation

- Subject must be able to swallow capsules

- Study eye must have best corrected visual acuity (BCVA) of 20/20-20/400

- Subject must be willing and able to pay for monthly prescription of Metformin HCl for
18 months in the event that their insurance carrier will not cover the cost of the
drug

Exclusion Criteria:

- Subjects with insufficient baseline size of geographic atrophy, less than 1.25 mm2
(0.5 Macular Photocoagulation Study Disc Areas). GA is defined as one or more
well-defined and often circular patches of partial or complete depigmentation of the
RPE, typically with exposure of underlying choroidal blood vessels. Even if much of
the RPE appears to be preserved and large choroidal vessels are not visible, a round
patch of RPE partial depigmentation may be classified as early GA. The GA in the study
eye must be able to be photographed in its entirety, and it must not be contiguous
with any areas of peripapillary atrophy, which can complicate area measurements.

- Subjects who are already taking metformin for another purpose

- Subjects with type 1 or 2 diabetes

- Subjects with compromised kidney function:

- Serum creatinine ≥1.5 mg/dL for males and ≥1.4 mg/dL for females

- Subjects with moderate to severe heart failure (Class III or IV, New York Heart
Association Functional Classifications)

- Subjects with Child's class C cirrhosis

- Evidence of retinal atrophy due to causes other than atrophic AMD.

- Subjects who have had anti-VEGF injections or active choroidal neovascularization in
the study eye during the last 12 months

- Current evidence or history of ocular disorders in the study eye that in the opinion
of the investigator confounds study outcome measures, including (but not limited to):

1. Non-proliferative diabetic retinopathy involving 10 or more hemorrhages or
microaneurysms, or active proliferative diabetic retinopathy

2. Branch or central retinal vein or artery occlusion

3. Macular hole

4. Pathologic myopia

5. Uveitis

6. Pseudovitelliform maculopathy

7. Intraoperative surgery within the last 90 days prior to study eye enrollment