Assessment of Safety, Tolerability and Pharmacokinetics of Intravitreal APL-2 Therapy for Neovascular Age-Related Macular Degeneration (AMD)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 4
- 主要终点
- Number of Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The objective of this study is to provide initial safety, tolerability and pharmacokinetics information of intravitreal administration of pegcetacoplan in order to support further development into larger Phase II studies for treatment of patients with AMD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Male or Female
- •Age ≥ 50 years
- •The presence of an active choroidal neovascular lesion secondary to AMD
- •On treatment with anti-VEGF therapy (Lucentis®, Eylea® or Avastin®)
- •Must have received at least 3 anti-VEGF treatments over the 26-week period prior to screening (Screening Visit)
- •Evidence that the macular fluid has responded to anti-VEGF in the past based on OCT in the opinion of PI
- •At screening, evidence of subretinal fluid and retinal cystic changes
- •Must have received anti-VEGF treatment within 10 days prior to pegcetacoplan treatment (anti-VEGF can be administered on the same day of the screening visit after the screening procedures have been completed)
- •OCTs of sufficient quality to allow for the assessment of the central macular fluid can be obtained
- •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
- •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
排除标准
- •Choroidal neovascularization associated with other ocular diseases such as pathologic myopia, ocular histoplasmosis or posterior uveitis, etc
- •Decreased vision due to retinal disease not attributable to choroidal neovascularization, such as nonexudative forms of AMD, geographic atrophy, inherited retinal dystrophy, uveitis or epiretinal membrane, a vitelliform-like lesion of the outer retina (e.g., as in pattern dystrophies or basal laminar drusen), idiopathic parafoveal telangiectasis, or central serous retinopathy
- •Additional ocular diseases that have irreversibly compromised or, during follow-up, could likely compromise the VA of the study eye including amblyopia, anterior ischemic optic neuropathy, clinically significant diabetic macular edema, severe non proliferative diabetic retinopathy, or proliferative diabetic retinopathy
- •Decreased vision due to significant media opacity such as corneal disease or cataract, or opacity precluding photography of the retina
- •Cataract surgery within three months of enrollment
- •Presence of any hemorrhage
- •History of treatment for CNV:
- •Previous PDT treatment within 30 days prior to enrollment in the study
- •Previous extrafoveal or juxtafoveal thermal laser photocoagulation within 30 days prior to enrollment in the study
- •Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization
- •Medical problems that make consistent follow-up over the treatment period unlikely (e.g. stroke, severe MI, end stage malignancy), or in general a poor medical risk because of other systemic diseases or active uncontrolled infections
- •Hypersensitivity to fluorescein
研究组 & 干预措施
Pegcetacoplan Cohort 1
4 mg of pegcetacoplan 100 μL IVT injection
干预措施: Pegcetacoplan (Drug)
Pegcetacoplan Cohort 2
10 mg of pegcetacoplan 100 μL IVT injection
干预措施: Pegcetacoplan (Drug)
Pegcetacoplan Cohort 3
20 mg of pegcetacoplan 100 μL IVT injection
干预措施: Pegcetacoplan (Drug)
结局指标
主要结局
Number of Dose Limiting Toxicities (DLTs)
时间窗: Day 1 to Day 15
The occurrence of any of the following AEs were considered DLTs: intraocular inflammation (vitritis or uveitis), endophthalmitis, sustained elevation of intraocular pressure ≥30 millimeters (mm) of mercury, and/or sustained loss of visual acuity ≥15 letters not attributable to the injection procedure or progression of disease.
Number of Subjects Who Experienced Ocular and Systemic Adverse Events (AEs), Including by Severity
时间窗: Day 1 to Day 113
Safety was assessed throughout the study. A TEAE was defined as any AE that started on/after the IVT injection of pegcetacoplan.
Median Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-t])
时间窗: Predose (screening), postdose Day 3 to Day 113
The AUC(0-t) was measured using the linear trapezoidal method when concentrations were increasing and the logarithmic trapezoidal method when concentrations were decreasing. The median AUC(0-t) is presented for each cohort.
Maximum Observed Serum Concentration (Cmax)
时间窗: Predose (screening), postdose Day 3 to Day 113
The median Cmax is presented for each cohort.
Median Dose Normalized Cmax
时间窗: Predose (screening), postdose Day 3 to Day 113
The dose normalized Cmax was calculated for each subject by dividing the parameter by the subject's respective dose in milligrams. The median dose normalized Cmax is presented for each cohort.
Median Dose Normalized AUC(0-t)
时间窗: Predose (screening), postdose Day 3 to Day 113
The AUC(0-t) was measured using the linear trapezoidal method when concentrations were increasing and the logarithmic trapezoidal method when concentrations were decreasing. The dose normalized AUC(0-t) was calculated for each subject by dividing the parameter by the subject's respective dose in milligrams. The median dose normalized AUC(0-t) is presented for each cohort.
Median Time to the Maximum Measured Serum Concentration (Tmax)
时间窗: Predose (screening), postdose Day 3 to Day 113
The median Tmax is presented for each cohort. If the maximum value occurred at more than 1 time point, Tmax was defined as the first time point with this value.
次要结局
- Median Change From Baseline in Visual Acuity for the Study Eye(Day 1 to Day 113)
- Median Change From Baseline in Central Retinal Thickness, Central Retinal Lesion Thickness and Central Subfield Thickness in the Study Eye(Day 1 to Day 113)
- Median Change From Baseline in Macular Cube Volume in the Study Eye(Day 1 to Day 113)