A Non-Randomized, Open Label, Safety and Efficacy Study Evaluating Kamuvudine-8 (K8) for the Treatment of Patients With Geographic Atrophy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 16
- 主要终点
- Adverse Events
研究概览
简要总结
This interventional study is a single-center, open label, 26-week study, designed to evaluate the safety and treatment efficacy of K8 in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD). Up to 5 subjects will receive study medication. Study treatment will be administered by intravitreal injections. Number of participants has been expanded to 30.
Participants will have 7 scheduled visits - Screening with baseline (injection), safety visit 2 days after injection, week 4, week 13 (injection), safety visit 2 days after injection, week 17, week 26.
Exams will look for continuous changes in visual acuity, change in area of geographic atrophy lesions in diagnostic imaging, response measured by multifocal electroretinogram, change in reading speed, and change in microperimetry response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 50 or older, diagnosed with geographic atrophy (GA) due to age-related macular degeneration (AMD).
- •Best corrected visual acuity (BCVA) 24 or greater Early Treatment of Diabetic Retinopathy Study (ETDRS) letters (approximately Snellen 20/320 or greater), in study eye.
- •The entire geographic atrophy (GA) lesion must be completely visualized on the macula centered image and must be able to be imaged in its entirety and not contiguous with any areas of peripapillary atrophy except in such cases where there is a "neck" or some narrow area connecting the GA with the peripapillary atrophy, as determined by Fundus Autofluorescence (FAF) imaging at screening:
- •Both eyes must have GA and the total GA area in each eye must be ≥ 2.5 and ≤ 20.0 mm2 (1 and 8 disk areas [DA] respectively)
- •If geographic atrophy (GA) is multifocal, at least one focal lesion must be ≥ 1.25 mm2 (0.5 DA), with the overall aggregate area of GA, as specified above.
- •If geographic atrophy (GA) is unifocal, then the lesion must be extrafoveal.
- •Presence of any pattern of hyperautofluorescence in the junctional zone of geographic atrophy (GA). Absence of hyperautofluorescence (i.e., pattern = none) is exclusionary.
- •Fundus Autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), or Fluorescein Angiography (FA) imaging of entire geographic atrophy (GA)lesion at least 6 months prior to entry.
排除标准
- •Females who are pregnant, nursing, planning a pregnancy or who are of childbearing potential not using a reliable method of contraception
- •History or current evidence of hypersensitivity to any components of the study medication or fluorescein, as assessed by the investigator
- •Participation in any investigational drug or device study within 30 days prior to baseline
- •History or current evidence of a medical condition or medication use that may, in the opinion of the investigator, preclude the safe administration of study medication or affect the results of the study
- •Participation in any systemic experimental treatment or any other systemic investigational new drug within 6 weeks or 5 half-lives of the active ingredient (whichever is longer) prior to the start of study treatment. Clinical trials solely involving observation, over-the-counter vitamins, supplements, or diets are not exclusionary.
- •Ocular Exclusion Criteria:
- •Active ocular or periocular infections, malignancy
- •History of major ophthalmic surgery in the past 3 months, and any ophthalmic surgery in study eye in the last 30 days
- •History of significant ocular disease other than AMD that may confound results
- •Any history or current evidence of exudative ("wet") AMD including any evidence of retinal pigment epithelium rips or evidence of retinal, choroidal, or peripapillary neovascularization in either eye
- •Known hypersensitivity to study drug or any of the excipients in implant
- •Macular atrophy secondary to a condition other than AMD
- •History of laser therapy in the macular region
- •Aphakia or surgically compromised/absent posterior capsule including presence of scleral fixated lenses. Note: YAG laser posterior capsulotomy for posterior capsule opacification done at least 60 days prior to screening is not exclusionary
- •History of prior posterior vitrectomy
- •History of prior intraocular gene therapy for any indication
- •History of extended hydroxychloroquine or pentosan polysulfate exposure (> 3 months)
- •Current use of medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine/hydroxychloroquine [Plaquenil®], tamoxifen, phenothiazines, ethambutol, digoxin, pentosan polysulfate, and aminoglycosides).
- •Uncontrolled glaucoma (defined as intraocular pressure >21mm Hg despite treatment with ocular hypotensive medications at baseline)
- •Prior participation in another interventional clinical study or treatment for GA in the study eye including topical, IVT, subretinal, suprachoroidal, periocular or oral medication or placebo within 5 half-lives of the active ingredient
- •Prohibited Medications/Treatments:
- •Systemic anti-VEGF medications
- •Intravitreal injections of Syfovre (pegcetacoplan), Izervay (avacincaptad pegol) or other complement inhibitors in either eye
- •Gene therapy injections in either eye
研究组 & 干预措施
Patients with geographic atrophy associated with age-related macular degeneration
Kamuvudine-8 treatment (0.3 mg) at baseline visit and week 13 visit, in one eye of each subject, for a total of up to 30 subjects. When new study drug is received, the next 20 patients will be enrolled to receive K8 treatment (either 0.7 mg or 1.05 mg) at baseline and week 13, in one eye of each subject, for a total of up to 30 subjects. The total of 30 patients is across three dosing groups. Once subjects have received one dose/type of implant, there is no crossover to a different group.
Patients will be followed for 26 weeks after baseline visit injection.
干预措施: K8 (Drug)
结局指标
主要结局
Adverse Events
时间窗: Within the study period (of 26 weeks)
Frequency of participants experiencing ocular or systemic adverse events.
Mean change in best-corrected visual acuity (BCVA)
时间窗: At baseline visit, week 13 visit, and week 26 visit
best-corrected visual acuity as defined by the number of letters read on the scale set by the ETDRS (Early Treatment of Diabetic Retinopathy Study). (More letters read equates to better visual acuity)
Adverse Events
时间窗: Within the study period (of 26 weeks)
Frequency of participants experiencing ocular or systemic adverse events.
Mean change in best-corrected visual acuity (BCVA)
时间窗: At baseline visit, week 13 visit, and week 26 visit
best-corrected visual acuity as defined by the number of letters read on the scale set by the ETDRS (Early Treatment of Diabetic Retinopathy Study). (More letters read equates to better visual acuity)
Mean change in low-luminance best-corrected visual acuity (ll-BCVA)
时间窗: At baseline visit, week 13 visit, and week 26 visit
best-corrected visual acuity in low-lighting settings
change in size of geographic atrophy (GA) on optical coherence tomography (OCT)
时间窗: At baseline visit, week 13 visit, and week 26 visit
Change in total area of geographic atrophy lesions as analyzed with OCT imaging
Change in size of geographic atrophy (GA) on fundus autofluorescence (FAF)
时间窗: At baseline visit, week 13 visit, and week 26 visit
Change in total area of geographic atrophy lesions as analyzed with FAF imaging over the course of the trial
Change in multifocal electroretinograms (mfERG) response
时间窗: At baseline visit, week 13 visit, and week 26 visit
Total response change measured by mfERG (performed upon site PI discretion and only if site has), which measures the electrical signal generated by a functionining eye processing information
Change in microperimetry response
时间窗: At baseline visit, week 13 visit, and week 26 visit
change in response to visual field testing with microperimetry (undilated) over the course of the study (performed upon site PI discretion and only if site has).
Change in reading speed
时间窗: At baseline visit, week 13 visit, and week 26 visit
Change in reading speed as measured by Radner reading chart procedure
Discontinued subjects
时间窗: This will be done at every scheduled visit and any unscheduled visit, as well as when reported by participants (for 26 weeks)
Number of subjects exiting study for any reason
change in size of geographic atrophy (GA) on fluorescein angiogram (FA)
时间窗: At baseline visit, week 13 visit, and week 26 visit
Change in total area of geographic atrophy lesions as analyzed with FA imaging
次要结局
- Change in best corrected visual acuity (BCVA) over multiple time points(Day 2 visit, Week 4 visit, Week 13 visit, Week 13 + 2 Days visit, and Week 17 visit)
研究者
Michelle Abou-Jaoude
Assistant Professor
University of Kentucky