Eye Diseases, Geographic Atrophy, Pathological Conditions, Anatomical, Retinal Degeneration, Retinal Diseases
Conditions
Keywords
Geographic Atrophy (GA), Age-related Macular Degeneration, AMD, SGLT2, Dapagliflozin
Brief summary
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.
Detailed 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: 1. Dapagliflozin 10 mg (oral) once daily 2. 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.
Interventions
DRUGDapagliflozin
Dapagliflozin is an SGLT2 inhibitor used in diabetes, heart failure, and chronic kidney disease patients.
OTHERMatching Placebo
Matching oral placebo to dapagliflozin
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants will be randomized 1:1 to either dapagliflozin or placebo and followed concurrently for 12 months. Two arms are defined: Experimental (Dapagliflozin 10 mg PO daily) and Placebo Comparator (matching placebo PO daily), with identical visit schedules for imaging and safety monitoring.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol 2. Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures 3. Participant is male or, if female, participant is surgically sterilized or amenorrheic for at least one year 4. ≥50 years old 5. Evidence of dry advanced AMD, including non-foveal GA or small foveal-involving GA, provided visual acuity criteria are met 1. The geographic atrophy may involve the fovea, provided the best-corrected visual acuity remains within protocol limits 2. Total area of geographic atrophy must be between 2.5 mm2 and 17.5 mm2 (1 - 4 disc areas, respectively). 3. 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). 6. BCVA between 20/25 and 20/320 7. Must be treatment-naïve for AMD in study eye, except for oral supplements
Exclusion criteria
1. Prior investigational drug use within 60 days 2. Use of other SGLT2 inhibitors 3. History of symptomatic hypotension or symptomatic hypotension (symptoms of hypotension + SBP \< 90mmHg) at baseline 4. Type I and Type II Diabetes Mellitus 5. End stage renal disease or estimated glomerular filtration rate less than 25 mL/min/1.73 m2 per MDRD calculation 6. History of heart failure 7. History of a serious hypersensitivity reaction to dapagliflozin or any of the excipients in FARXIGA 8. 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 1. Any prior intravitreal treatment for any indication in the study eye. 2. Prior intravitreal treatment (steroids, anti-VEGF) in the fellow eye is permitted if all injections occurred more than 6 months prior to screening, provided the participant has no active intravitreal treatment in either eye at screening or during the study period 3. Prior exposure to complement inhibitor therapy for retinal disease in either eye at any time remains exclusionary 9. Any intraocular surgery or thermal laser within 3 months of date of randomization 10. Any ocular or periocular infection (including blepharitis), or ocular surface inflammation in the past 12 weeks 11. Any prior thermal laser in the macular region, regardless of indication (self-report) 12. Any evidence of choroidal neovascularization in study eye 13. Enrollment in another interventional trial during the trial period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Square Root GA Lesion Size in the Study Eye at Month 12 | Baseline (screening) and Month 12. | The square root GA lesion size (i.e. transformed area of GA) was measured by FAF photographs at baseline and 12 months. Baseline is defined as the last available, non-missing observation prior to first study drug administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Drusen Size in the Study Eye at Month 12 | Baseline (screening) and Month 12. | The mean change in size of drusen volume measured by OCT from Baseline to Month 12 |
| Mean Change From Baseline in best corrected visual acuity (ETDRS letters) from Baseline to Month 12 | Baseline (screening) and Month 12. | The mean change in best corrected visual acuity (ETDRS letters) from Baseline to Month 12 |
| Mean Change From Baseline in Dark Adaptation in the Study Eye at Month 12 | Baseline (screening) and Month 12. | The mean change in rod intercept time on dark adaptation from Baseline to Month 12 |
| Mean Change From Baseline in low luminance best corrected visual acuity (ETDRS letters) from Baseline to Month 12 | Baseline (screening) and Month 12. | The mean change in low luminance best corrected visual acuity (ETDRS letters) from Baseline to Month 12 |
Countries
United States
Contacts
CONTACTEve Adcock
PRINCIPAL_INVESTIGATORRajendra S Apte, MD PhD
Washington University School of Medicine
Outcome results
None listed