Overview
AMD is a leading cause of blindness in individuals over 50 years old, with dry AMD being the most common form. Geographic atrophy (GA) is an advanced stage of dry AMD characterized by progressive retinal cell degeneration. The primary objectives of the study are to assess the safety, tolerability, and evidence of activity of SGLT2 inhibitors in subjects with Geographic Atrophy associated with AMD.
Description
This is a Phase II, prospective, single-center, randomized, double-blind, placebo-controlled study to assess the safety, tolerability, and efficacy of oral dapagliflozin in subjects with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
The study will randomize approximately 70 subjects to obtain at least 60 evaluable subjects at a single center site.
Subjects will be randomized in a 1:1 manner to receive:
- Dapagliflozin 10 mg (oral) once daily
- Matching placebo (oral) once daily
Primary outcome of interest will be progression of GA lesion area over the 1-year period measured by fundus autofluorescence (FAF) , and secondary outcomes include structural and functional testing for visual function such as change in drusen volume as measured by OCT, dark adaptation, and low luminance BCVA to determine the effect of dapagliflozin on the progression of dry AMD.
All subjects will return for a final follow-up visit at Month 12, marking the conclusion of the study.
Eligibility
Inclusion Criteria:
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
- Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
- Participant is male or, if female, participant is surgically sterilized or amenorrheic for at least one year
- ≥50 years old
- Evidence of dry advanced AMD with the presence of non-foveal Geographic Atrophy (GA)
- The geographic atrophy must not involve the center point of the fovea.
- Total area of geographic atrophy must be between 2.5 mm2 and 17.5 mm2 (1 - 4 disc areas, respectively).
- If the geographic atrophy consists of multiple lesions, at least one lesion must have an area of ≥1.25 mm² (equivalent to 0.5 disc areas).
- BCVA between 20/25 and 20/320
- Must be treatment-naïve for AMD, except for oral supplements
Exclusion Criteria:
- Prior investigational drug use within 60 days
- Use of other SGLT2 inhibitors
- History of symptomatic hypotension or symptomatic hypotension (symptoms of hypotension + SBP < 90mmHg) at baseline
- Type I and Type II Diabetes Mellitus
- End stage renal disease or estimated glomerular filtration rate less than 25 mL/min/1.73 m2 per MDRD calculation
- History of heart failure
- History of a serious hypersensitivity reaction to dapagliflozin or any of the excipients in FARXIGA
- Other concomitant disease or condition that investigator deems unsuitable for the study, including drug or alcohol abuse or psychiatric, behavioral, or cognitive disorders, sufficient to interfere with the patient's ability to understand and comply with the study instructions or follow-up procedures
- Any prior treatment for AMD (dry or wet) or any prior intravitreal treatment for any indication in either eye, except oral supplements of vitamins or mineral
- Any intraocular surgery or thermal laser within 3 months of date of randomization
- Any ocular or periocular infection (including blepharitis), or ocular surface inflammation in the past 12 weeks
- Any prior thermal laser in the macular region, regardless of indication (self-report)
- Any evidence of choroidal neovascularization in study eye
- Enrollment in another interventional trial during the trial period