Alpha Lipoic Acid in Geographic Atrophy

Phase I (Apr 2016 completed): 15 subjects, 65 years of age or older will take alpha lipoic
acid on the following schedule:

600 mg once daily with a meal for 5 days. If tolerated, then the subject will then take 800
mg once daily with a meal for 5 days.

If tolerated, then the subject will then take 1200 mg once daily with a meal for 5 days.

Phase II: Randomized, double-blind placebo controlled pilot trial. Upon the completion of the
dose tolerability test, we plan to enroll 50 subjects into a randomized, double-blind,
placebo-controlled trial. Subjects will be randomized (1:1) into one of two study arms:
placebo capsules and ALA 1200 mg orally once daily, assuming that 1200 mg is well tolerated
by subjects in Phase 1. If 1200 mg is not well-tolerated based on Phase 1 data, then the
highest tolerable dose will be used. Four clinical sites are planned and the enrollment
period is estimated to be 6 months. The primary endpoint is the mean rate of change of the
area of GA in the study eye from baseline to 18 months as evaluated by fundus
autofluorescence. Subjects will have a refracted electronic visual acuity and dilated exam at
baseline, 6 months, 12 months, and 18 months. The study will be conducted on an outpatient
basis and study visits will last approximately 2-3 hours. Two weeks after the 18 months study
visit, the subject will be contacted to share with the investigators adverse events that
developed after completing the 18 month visit. The Investigator shall ensure each subject has
a follow-up eye exam scheduled within 6 months.

Phase I

Inclusion Criteria:

- Ages 65-90

- Female participants must be menopausal. Male participants are required to use
contraception.

- Able to give informed consent

- For the study duration (15 days), the subject must remain in the country, remain
within 4 hours of travel time (by car or airplane), have access to medical care if
needed, and provide contact information so the subject can be reached as needed.

Exclusion Criteria:

- Blood Pressure greater than 190/100 at the baseline visit

- Pulse greater than 100 at the baseline visit

- Acute and ongoing systemic infection

- History of dementia

- Participant has a condition that, in the opinion of the investigator, gives them an
unstable medical status.

- Participant has geographic atrophy and the investigator believes the participant is a
candidate for enrollment into the planned Phase 2 trial for geographic atrophy.

Phase II

Inclusion Criteria

- Age 55-90

- • Diagnosis of geographic atrophy from age-related macular degeneration in the study
eye. The largest GA lesion must be a minimum of 0.5 DA (1.25 mm2) and no more than 6
DA in size (15.0 mm2). GA is defined as one or more well-defined, usually more or less
circular patches of loss of the RPE, typically with exposure of underlying choroidal
blood vessels. If the GA is multifocal and the largest lesion is < 0.5 DA, then there
should be at least 3 lesions ≥ 250 microns in greatest linear diameter.

- BCVA between 20/20 and 20/400 in the study eye.

- Female participants must be menopausal. Male participants are required to use
contraception and cannot donate sperm during study participation.

- Presence of hyperfluorescence at the edge of GA on autofluorescence imaging.

- Ability to give informed consent.

- If a subject has two eligible eyes, then both eyes can be enrolled into the study.

- Subject must have mailed back the medication bottle after the 10 day run-in phase,
demonstrating that they have taken ≥ 80% of the capsules.

Exclusion Criteria

- Evidence of ocular disease other than AMD in the study eye that may confound the study
outcomes (e.g., History of myopic degeneration, choroidal neovascularization, central
serous chorioretinopathy, severe diabetic retinopathy, uveitis, vitelliform dystrophy,
or macular edema).

- Presence of geographic atrophy that is already touching clearly defined beta
peripapillary atrophy or is already touching the optic disc. Beta peripapillary
atrophy is defined as peripapillary atrophy in which either the sclera or choroidal
vessels are clearly visible.

- Any history of intravitreal injection in the study eye for AMD or choroidal
neovascularization.

However, if a subject develops choroidal neovascularization in the study eye during the
study, then the subject will receive the standard of care intravitreal injection treatments
per the investigator. The subject will continue to stay in the study. Treatment of CNV or
other diseases in the non-study eye is at the investigator's discretion.

- History of intravitreal injection of any agent (e.g., triamcinolone) other than
anti-VEGF in the study eye within the last four months prior to study enrollment.

- History of laser treatment (including photodynamic therapy) to the macula for the
study eye.

- History of intraocular surgery within 90 days. for the study eye.

- History of anterior segment laser (laser peripheral idotomyiridotomy, laser to
trabecular meshwork, YAG capsulotomy) within 90 days for the study eye.

- Media opacity (corneal scar, cataract) that would prevent adequate fundus imaging for
the study eye.

- Any history of participation in another therapeutic clinical trial for GA.

- Participation currently or within the past 30 days in another therapeutic clinical
trial in which a systemic or ocular study medication is received by the subject.

- GA in the study eye due to a cause other than AMD

- History of prior use of ALA.

- AREDS (Age Related Eye Disease Study) vitamins taken at standard doses are not
considered an exclusion criterion. Taking a standard multivitamin is not considered an
exclusion criterion. However, the multivitamin should not contain alpha lipoic acid
(also known as thioctic acid).

- Taking antioxidant supplements other than a standard multivitamin (such as bilberry,
vitamin C that is not part of a multivitamin or taken at higher doses than the AREDS
formula, vitamin E that is not part of a multivitamin or taken at higher doses than
the AREDS formula, or other similar antioxidants) within one month of enrollment is an
exclusion criteria; these patients should discontinue the antioxidant supplement one
month before enrollment in order to participate. Taking a supplement that has
antioxidant potential that is recommended by a physician as standard-of-care medical
management is not an exclusion criterion.).

- Participant has a condition that, in the opinion of the investigator, would preclude
participation in the study for 18 months (e.g., unstable medical status including
blood pressure and glycemic control, unstable psychiatric history, moving and not able
to return for all planned study visits).

- History of a formal diagnosis of dementia by a neurologist.

- History of gastric ulcer within the past 5 years.

- History of irritable bowel syndrome within the past 5 years.