NCT03525613已完成3 期
A Phase 3, Multi-Center, Randomized, Double-Masked, Sham-Controlled Study to Compare the Efficacy and Safety of Intravitreal Pegcetacoplan Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 637
- 试验地点
- 111
- 主要终点
- Least Squares (LS) Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 12
研究概览
简要总结
This is a 24-month, Phase III, multicenter, randomized, double-masked, sham-injection controlled study to assess the efficacy and safety of multiple IVT injections of APL-2 in subjects with GA secondary to 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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The study eye must meet all inclusion criteria. If both eyes meet the inclusion criteria, the eye with the worst visual acuity at the screening visit will be designated as the study eye. If both eyes have the same visual acuity, the right eye will be selected as the study eye.
- •Ocular- specific inclusion criteria apply to the study eye only, unless otherwise specified.
- •Age ≥ 60 years.
- •Normal Luminance best corrected visual acuity of 24 letters or better using Early Treatment Diabetic Retinopathy Study (ETDRS) charts (approximately 20/320 Snellen equivalent).
- •Clinical diagnosis of GA of the macula secondary to AMD as determined by the Investigator and confirmed by the Reading Center.
- •The GA lesion must meet the following criteria as determined by the central reading center's assessment of Fundus Autofluorescence (FAF) imaging at screening:
- •Total GA area must be ≥ 2.5 and ≤ 17.5 mm2 (1 and 7 disk areas [DA] respectively)
- •If 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 in 4a.
- •The entire 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.
- •Presence of any pattern of hyperautofluorescence in the junctional zone of GA. Absence of hyperautofluorescence (i.e. pattern = none) is exclusionary.
- •Adequate clarity of ocular media, adequate pupillary dilation, and fixation to permit the collection of good quality images as determined by the Investigator.
- •Meets the following criteria related to microperimetry:
- •Able to detect fixation target.
- •Total elapsed time to complete the 10-2 68 point exam is ≤ 30 minutes in duration.
- •Reliability test ratio must be ≤ 20%.
- •Subject is willing and able to undertake microperimetry assessment in the opinion of the investigator.
- •Female subjects must be:
- •Women of non-child-bearing potential (WONCBP), or
- •Women of child-bearing potential (WOCBP) with a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study and refrain from breastfeeding for the duration of the study.
- •Males with female partners of child-bearing potential must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study.
- •Willing and able to give informed consent and to comply with the study procedures and assessments.
排除标准
- •Ocular specific exclusion criteria apply to the study eye only, unless otherwise specified.
- •GA secondary to a condition other than AMD such as Stargardt disease, cone rod dystrophy or toxic maculopathies like plaquenil maculopathy in either eye.
- •Spherical equivalent of the refractive error demonstrating > 6 diopters of myopia or an axial length >26 mm.
- •Any history or active choroidal neovascularization (CNV), associated with AMD or any other cause, including any evidence of retinal pigment epithelium rips or evidence of neovascularization anywhere based on SD-OCT imaging and/or fluorescein angiography as assessed by the Reading Center.
- •Presence of an active ocular disease that in the opinion of the Investigator compromises or confounds visual function, including but not limited to, uveitis, other macular diseases (e.g. clinically significant epiretinal membrane (ERM), full thickness macular hole or uncontrolled glaucoma/ocular hypertension. Benign conditions in the opinion of the investigator such as peripheral retina dystrophy are not exclusionary).
- •Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization.
- •History of laser therapy in the macular region.
- •Aphakia or absence of the posterior capsule. Note: YAG laser posterior capsulotomy for posterior capsule opacification done at least 60 days prior to screening is not exclusionary.
- •Any ocular condition other than GA secondary to AMD that may require surgery or medical intervention during the study period or, in the opinion of the Investigator, could compromise visual function during the study period.
- •Any contraindication to IVT injection including current ocular or periocular infection.
- •History of prior intravitreal injection.
- •Unable to perform microperimetry reliably in the opinion of the investigator
- •Prior participation in another interventional clinical study for intravitreal therapies in either eye (including subjects receiving sham).
- •Prior participation in another interventional clinical study for geographic atrophy in either eye including investigational oral medication and placebo.
- •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. Note: clinical trials solely involving observation, over-the-counter vitamins, supplements, or diets are not exclusionary.
- •Medical or psychiatric conditions that, in the opinion of the investigator, make consistent follow-up over the 24-month treatment period unlikely, or would make the subject an unsafe study candidate.
- •Any screening laboratory value (hematology, serum chemistry or urinalysis) that in the opinion of the Investigator is clinically significant and not suitable for study participation.
- •Known hypersensitivity to fluorescein sodium for injection or hypersensitivity to APL-2 or any of the excipients in APL-2 solution.
研究组 & 干预措施
APL-2 15mg 0.1 mL Monthly for 24 months
Experimental
A single dose of 15 mg APL-2/0.1 mL will be administered via intravitreal injection in this study. Subjects will receive an injection every month
干预措施: APL-2 (Drug)
APL-2 15mg 0.1 mL EOM for 24 months
Experimental
A single dose of 15 mg APL-2/0.1 mL will be administered via intravitreal injection in this study. Subjects will receive an injection every other month
干预措施: APL-2 (Drug)
Sham Procedure Monthly for 24 months
Experimental
Sham Procedure monthly for 24 months
干预措施: Sham Procedure (Other)
Sham Procedure Every Other Month for 24 months
Experimental
Sham Procedure every other month for 24 months
干预措施: Sham Procedure (Other)
结局指标
主要结局
Least Squares (LS) Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 12
时间窗: Baseline (screening) and Month 12
The GA lesion area was measured by a quantified central reading center based on FAF images. LS mean was calculated using a mixed effect model for repeated measure (MMRM) model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.
次要结局
- LS Mean Change From Baseline in Monocular Maximum Reading Speed of the Study Eye at Month 24(Baseline (screening) and Month 24)
- LS Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 24(Baseline (screening) and Month 24)
- LS Mean Change From Baseline in Mean Threshold Sensitivity of All Points of the Study Eye at Month 24(Baseline (screening) and Month 24)
- Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24(From Baseline (screening) through Month 24)
- LS Mean Change From Baseline in Mean Functional Reading Independence (FRI) Index Score at Month 24(Baseline (screening) and Month 24)
- LS Mean Change From Baseline in Normal-Luminance Best-Corrected Visual Acuity (NL-BCVA) Score of the Study Eye at Month 24(Baseline (screening) and Month 24)
研究者
研究点 (111)
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