A Multicenter, Multiple-Dose Study in Neovascular Age-related Macular Degeneration (nAMD) to Evaluate the Safety, Tolerability, Pharmacodynamics, Immunogenicity, and Clinical Effect of Repeat Intravitreal (IVT) Injections of GEM103 as an Adjunct to Standard of Care Aflibercept Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 50
- 试验地点
- 23
- 主要终点
- Number of Participants With Non-ocular TEAEs
研究概览
简要总结
This study is designed to investigate the safety and tolerability of GEM103 IVT injection + standard of care vs. sham + standard of care.
详细描述
This is a Phase 2a, multi-center, multiple dose study in subjects with Neovascular Age-related Macular Degeneration (nAMD) to investigate the safety and tolerability of GEM103 IVT injection + standard of care vs. sham + standard of care.
Subjects will undergo clinical and ophthalmic assessments for determination of inclusion in the study and who meet all eligibility criteria will be enrolled.
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
- Single (Participant)
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
- •At least 50 years old at the time of signed informed consent
- •Choroidal neovascularization (CNV) related to nAMD with the following features, as determined by the Image Reading Center
- •Maximum CNV lesion size of 12 disc areas
- •Subretinal hemorrhage less than or equal to (<=) 50% of lesion size
- •On aflibercept treatment prior to Day 1
- •Best Corrected Visual Acuity (BCVA) in the study eye between 24 to 75 letters using EDTRS
排除标准
- •Presence of the following ocular conditions in the study eye:
- •Any active ocular disease or condition that impact the subject to participate in the study or be a contraindication of IVT injections
- •Any intraocular surgery
- •Aphakia or complete absence of the posterior capsule
- •Prior corneal transplant
- •Scar or fibrosis greater than or equal to (>=) 50% of CNV lesion or involving center of fovea
- •Presence of any of the following ocular conditions in either eye:
- •History of herpetic infection, idiopathic polypoidal choroidal vasculopathy (PCV), pathologic myopia, central serous chorioretinopathy (CSCR), adult onset foveal pattern dystrophy
- •Concurrent disease that could require medical or surgical intervention during the study period
- •Active/suspected ocular/periocular infection or active intraocular inflammation
- •History of idiopathic or autoimmune-associated uveitis
- •Any prior or ongoing medical condition or clinically significant screening laboratory value that may present a safety risk, interfere with study compliance, interfere with consistent study follow-up, or confound data interpretation throughout the longitudinal follow-up period
- •Has experienced a cardiovascular or cerebrovascular event within 12 months of informed consent
- •Females must not be pregnant or lactating
- •Current use of medications known to be toxic to the lens, retina or optic nerve
- •Use of any investigational new drug or other experimental treatment in the last 6 months prior to Day 1, and/or receipt of any prior gene therapy or ocular device implantation
研究组 & 干预措施
SoC + GEM103
Participants were administered SoC therapy defined as aflibercept (2 milligram [mg]/50 microliter [mcL]) first, followed by GEM103 (500 microgram [mcg]/50mcL) 15 minutes later. Administration occurred every other month (EOM) for a total of 6 doses during the 12-month study period.
干预措施: GEM103 (Biological)
SoC + GEM103
Participants were administered SoC therapy defined as aflibercept (2 milligram [mg]/50 microliter [mcL]) first, followed by GEM103 (500 microgram [mcg]/50mcL) 15 minutes later. Administration occurred every other month (EOM) for a total of 6 doses during the 12-month study period.
干预措施: Aflibercept (Drug)
SoC + Sham
Participants were administered SoC therapy defined as aflibercept (2mg/50mcL) first, followed by the Sham injection 15 minutes later. Administration occurred EOM for a total of 6 doses during the 12-month study period.
干预措施: Aflibercept (Drug)
SoC + Sham
Participants were administered SoC therapy defined as aflibercept (2mg/50mcL) first, followed by the Sham injection 15 minutes later. Administration occurred EOM for a total of 6 doses during the 12-month study period.
干预措施: Sham (Drug)
结局指标
主要结局
Number of Participants With Non-ocular TEAEs
时间窗: Baseline up to Week 48
An adverse event (AE) was defined as any untoward medical occurrence or worsening of a pre-existing condition in a participant administered a pharmaceutical product during the study, whether related or not to the study medication. TEAEs were defined as AE that occurred on or after the date and time of study drug administration or those that first occurred pre-dose but worsened by increase in occurrence or severity after study drug administration. Number of participants with non-ocular TEAEs were reported.
Number of Participants With Ocular Treatment-emergent Adverse Events (TEAEs)
时间窗: Baseline up to Week 48
An adverse event (AE) was defined as any untoward medical occurrence or worsening of a pre-existing condition in a participant administered a pharmaceutical product during the study, whether related or not to the study medication. TEAEs were defined as AE that occurred on or after the date and time of study drug administration or those that first occurred pre-dose but worsened by increase in occurrence or severity after study drug administration. Number of participants with ocular TEAEs in study eye and fellow eye were reported.
Number of Participants With Abnormal Ophthalmic Examination Findings
时间窗: Baseline up to Week 48
Ophthalmoscopy examination was performed in each eye with findings reported for Vitreous, Optic Nerve, Macula, Retina Periphery. Lens Status and Opacification (Phakic and Pseudophakic) was also performed. Nuclear Cataract, Cortical Cataract, and Posterior Subcapsular Cataract categories was further summarized by severity grade. Ocular biomicroscopic examination was performed with findings reported for Lids/Lashes, Conjunctiva, Cornea, Anterior Chamber, and Iris/Pupil.
Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Low Luminance Visual Acuity (LLVA)
时间窗: Baseline up to Week 48
Visual function assessments included LLVA assessment in each eye by ETDRS letters. LLVA was measured on the ETDRS chart at a starting distance of 4 meters. The letter score ranges from 0 (worse score) to 100 (best score), and a gain in LLVA from baseline indicates an improvement in visual acuity. For each participant, an average value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. The results were summarized as the percentage of participants with increase in LLVA with \>=15, \>=10, \>=5 letters from the baseline per treatment arm who met the endpoint.
Mean Change From Baseline in Minnesota Low-vision Reading (MNRead) Test at Week 48
时间窗: Baseline, Week 48
The MNRead acuity cards are continuous-text reading acuity cards suitable for measuring the reading acuity and reading speed of normal and low-vision participants. Formula for reading speed words per minute (wpm): reading speed is equal to 60\*(10 - errors)/ (time in seconds). A negative change from baseline indicates a decrease in the reading speed; disease worsening.
Percentage of Participants With Greater Than or Equal to (>=)15, >=10, >=5 Letters From the Baseline in Best Corrected Visual Acuity (BCVA)
时间窗: Baseline up to Week 48
Visual function assessments included BCVA assessment in each eye by Early Treatment Diabetic Retinopathy Study (ETDRS) letters. BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The letter score ranges from 0 (worse score) to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. The results were summarized as the percentage of participants with increase in BCVA with greater than or equal to (\>=)15, \>=10, \>=5 letters from the baseline per treatment arm who met the endpoint.
次要结局
- Mean Change From Baseline in Macular Atrophy (MA) Assessed by Fundus Autofluorescence (FAF)(Baseline up to Week 48)
- Change From Baseline in Total Complement Factor H (CFH) Concentration in Aqueous Humor(Baseline, Week 32)
- Mean Change From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) at Week 48(Baseline, Week 48)