Wykoff Charles C, Campochiaro Peter A, Pieramici Dante J, Khanani Arshad M, Gune Shamika, Maia Mauricio, Kågedal Matts, Ding Han Ting, Maass Katie F
Retina Consultants of Texas, 4460 Bissonnet Street, Suite 200, Bellaire, TX, 77401, USA.
Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ophthalmol Ther. 2022 Oct;11(5):1705-1717. doi: 10.1007/s40123-022-00532-9. Epub 2022 Jun 27.
Ladder was a phase 2 trial that evaluated the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration. Serum and aqueous humor samples were collected to characterize the pharmacokinetics (PK) of ranibizumab delivered through the PDS.
Ladder was a multicenter, randomized, active treatment-controlled, phase 2 clinical trial. Patients with neovascular age-related macular degeneration (n = 220) were randomized (3:3:3:2) to PDS 10 mg/ml, PDS 40 mg/ml, PDS 100 mg/ml, or monthly intravitreal ranibizumab 0.5 mg. Serum PK samples were collected in all arms and analyzed for ranibizumab concentration using an enzyme-linked immunosorbent assay. The main PK analyses were conducted in the PK-evaluable population (n = 68), which excluded patients who received fellow eye intravitreal treatment, supplemental ranibizumab treatment, or had previous treatment with bevacizumab in either eye within 9 months of randomization.
In the PDS 10 mg/ml arm, median serum ranibizumab concentrations were below the serum trough concentration (C; 130 pg/ml) expected with monthly intravitreal ranibizumab 0.5 mg at all time points. In the PDS 40 mg/ml and 100 mg/ml arms, median serum ranibizumab concentrations were above the C expected with monthly intravitreal ranibizumab 0.5 mg (130 pg/ml) through month 3 and month 12 after implantation, respectively, and remained above the lower limit of quantification through month 15 and month 16 after implantation, respectively.
These PK data indicate that the implant in the PDS 100 mg/ml arm maintained ranibizumab concentrations within the range of monthly intravitreal ranibizumab 0.5 mg injections (130-2220 pg/ml) through month 12 after implantation.
ClinicalTrials.gov identifier, NCT02510794.
Ladder是一项2期试验，评估了用于新生血管性年龄相关性黄斑变性的雷珠单抗玻璃体内植入系统（PDS）。收集血清和房水样本以表征通过PDS递送的雷珠单抗的药代动力学（PK）。
Ladder是一项多中心、随机、活性药物对照的2期临床试验。将新生血管性年龄相关性黄斑变性患者（n = 220）随机分组（3:3:3:2），分别接受10 mg/ml PDS、40 mg/ml PDS、100 mg/ml PDS或每月一次玻璃体内注射0.5 mg雷珠单抗治疗。在所有治疗组中收集血清PK样本，并使用酶联免疫吸附测定法分析雷珠单抗浓度。主要PK分析在PK可评估人群（n = 68）中进行，该人群排除了接受对侧眼玻璃体内治疗、补充雷珠单抗治疗或在随机分组后9个月内任一眼曾接受贝伐单抗治疗的患者。
在10 mg/ml PDS治疗组中，所有时间点的血清雷珠单抗浓度中位数均低于每月一次玻璃体内注射0.5 mg雷珠单抗预期的血清谷浓度（C；130 pg/ml）。在40 mg/ml PDS和100 mg/ml PDS治疗组中，血清雷珠单抗浓度中位数在植入后第3个月和第12个月分别高于每月一次玻璃体内注射0.5 mg雷珠单抗预期的C（130 pg/ml），并在植入后第15个月和第16个月分别保持高于定量下限。
这些PK数据表明，100 mg/ml PDS治疗组中的植入物在植入后12个月内将雷珠单抗浓度维持在每月一次玻璃体内注射0.5 mg雷珠单抗的浓度范围内（130 - 2220 pg/ml）。
ClinicalTrials.gov标识符，NCT02510794。
