A Phase IIIb Study to Evaluate the Safety of Ranibizumab in Subjects with Neovascular Age-related Macular Degeneration
A Phase IIIb Study to Evaluate the Safety of Ranibizumab in Subjects with Neovascular Age-related Macular Degeneration
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DOI：
10.1016/j.ophtha.2009.05.024
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发表时间：
2009-09-01
期刊：
影响因子：
13.7
通讯作者：
Rubio, Roman G.
中科院分区：
文献类型：
--
作者：
Boyer, David S.;Heier, Jeffrey S.;Rubio, Roman G.
目的：评价玻璃体内注射雷珠单抗治疗大量新生血管性年龄相关性黄斑变性（AMD）患者的安全性和有效性。（队列1）或开放标签（第2组）多中心临床试验参与者：总共4300名患有血管造影确定的继发于AMD的中心凹下脉络膜新生血管（CNV）的受试者。1例接受0.3 mg（n = 1169）或0.5 mg（n = 1209）玻璃体内雷珠单抗3个月负荷剂量。根据AMD治疗史（初治vs.既往治疗）对剂量组进行分层。队列1受试者根据光学相干断层扫描（OCT）或视力（VA）标准重新接受治疗。队列2受试者（n = 1922）接受初始玻璃体内剂量为0.5 mg的雷珠单抗，并根据医生判断重新治疗。主要结果测量：安全性结果包括眼部和非眼部不良事件（AE）和严重不良事件（SAE）的发生率。疗效结果包括最佳矫正VA随时间的变化。结果：约81.7%的队列1受试者和49.9%的队列2受试者完成了12个月的研究。队列1的平均雷珠单抗注射总数为4.9，队列2为3.6。12个月研究期间，队列1 0.3 mg组的血管性和非血管性死亡发生率分别为0.9%和0.7%，队列1 0.5 mg组为0.8%和1.5%，队列2为0.7%和0.9%。队列1剂量组和队列2中不明原因死亡的发生率均为0.1%。各队列或剂量组间血管性死亡和不明原因死亡的数量无差异。0.3 mg和0.5 mg组以及队列2的卒中发生率分别为0.7%、1.2%和0.6%。在第12个月，第1组未接受过治疗的受试者平均获得了0.5（0.3 mg）和2.3（0.5 mg）VA字母，先前接受过治疗的受试者获得了1.7（0.3 mg）和2.3（0.5 mg）VA字母。雷珠单抗对VA具有有益作用。未来的研究将寻求为新生血管性AMD患者建立最佳的给药方案。
Objective: To evaluate the safety and efficacy of intravitreal ranibizumab in a large population of subjects with neovascular age-related macular degeneration (AMD).Design: Twelve-month randomized (cohort 1) or open-label (cohort 2) multicenter clinical trial.Participants: A total of 4300 subjects with angiographically determined subfoveal choroidal neovascularization (CNV) secondary to AMD.Methods: Cohort 1 subjects were randomized 1:1 to receive 0.3 mg (n = 1169) or 0.5 mg (n = 1209) intravitreal ranibizumab for 3 monthly loading doses. Dose groups were stratified by AMD treatment history (treatment-naive vs. previously treated). Cohort 1 subjects were retreated on the basis of optical coherence tomography (OCT) or visual acuity (VA) criteria. Cohort 2 subjects (n = 1922) received an initial intravitreal dose of 0.5 mg ranibizumab and were retreated at physician discretion. Safety was evaluated at all visits.Main Outcome Measures: Safety outcomes included the incidence of ocular and nonocular adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes included changes in best-corrected VA over time.Results: Some 81.7% of cohort 1 subjects and 49.9% of cohort 2 subjects completed the 12-month study. The average total number of ranibizumab injections was 4.9 for cohort 1 and 3.6 for cohort 2. The incidence of vascular and nonvascular deaths during the 12-month study was 0.9% and 0.7% in the cohort 1 0.3 mg group, 0.8% and 1.5% in the cohort 1 0.5 mg group, and 0.7% and 0.9% in cohort 2, respectively. The incidence of death due to unknown cause was 0.1% in both cohort 1 dose groups and cohort 2. The number of vascular deaths and deaths due to unknown cause did not differ across cohorts or dose groups. Stroke rates were 0.7%, 1.2%, and 0.6% in the 0.3 mg and 0.5 mg groups and cohort 2, respectively. At month 12, cohort 1 treatment -naive subjects had gained an average of 0.5 (0.3 mg) and 2.3 (0.5 mg) VA letters and previously treated subjects had gained 1.7 (0.3 mg) and 2.3 (0.5 mg) VA letters.Conclusions: Intravitreal ranibizumab was safe and well tolerated in a large population of subjects with neovascular AMD. Ranibizumab had a beneficial effect on VA. Future investigations will seek to establish optimal dosing regimens for persons with neovascular AMD.