Efficacy of Dapagliflozin in the Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Mean Change From Baseline in Square Root GA Lesion Size in the Study Eye at Month 12
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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, including non-foveal GA or small foveal-involving GA, provided visual acuity criteria are met
- •The geographic atrophy may involve the fovea, provided the best-corrected visual acuity remains within protocol limits
- •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 in study eye, except for oral supplements
排除标准
- •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 intravitreal treatment for any indication in the study eye.
- •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
- •Prior exposure to complement inhibitor therapy for retinal disease in either eye at any time remains exclusionary
- •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
研究组 & 干预措施
Dapagliflozin 10 mg daily for 12 months
Dapagliflozin 10 mg daily PO for 12 consecutive months
干预措施: Dapagliflozin (Drug)
Matching Placebo for 12 months
Subjects will receive a placebo medication daily PO for 12 consecutive months
干预措施: Matching Placebo (Other)
结局指标
主要结局
Mean Change From Baseline in Square Root GA Lesion Size in the Study Eye at Month 12
时间窗: 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.
次要结局
- Mean Change From Baseline in Drusen Size in the Study Eye at Month 12(Baseline (screening) and Month 12.)
- Mean Change From Baseline in best corrected visual acuity (ETDRS letters) from Baseline to Month 12(Baseline (screening) and Month 12.)
- Mean Change From Baseline in Dark Adaptation in the Study Eye at Month 12(Baseline (screening) and 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.)
研究者
Rajendra S. Apte
Principal Investigator; Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences; Vice Chair for Innovation and Translation
Washington University School of Medicine