PURPOSE

To evaluate the safety and tolerability of single and multiple intravitreal injections of NGM621 in patients with geographic atrophy (GA) and to characterize the pharmacokinetics and immunogenic potential.

DESIGN

Multicenter, open-label, single- and multiple-dose phase 1 study.

METHODS

Fifteen patients enrolled at 4 sites in the United States. Participants had GA secondary to age-related macular degeneration, lesion size ≥2.5 mm², best-corrected visual acuity of 4 to 54 letters (20/80 to 20/800 Snellen equivalent) in the study eye, and no history of choroidal neovascularization in either eye. Patients who met eligibility criteria were treated in a single ascending-dose phase (2 mg, 7.5 mg, and 15 mg) or received 2 doses of NGM621 (15 mg) 4 weeks apart in the multidose phase and were monitored for 12 weeks (85 days). Assessments included adverse events, best-corrected visual acuity, low-luminance visual acuity, vital signs, clinical laboratory evaluations, GA lesion area as measured by fundus autofluorescence, spectral domain optical coherence tomography, and pharmacokinetic, immunogenicity, and pharmacodynamic assessments.

RESULTS

All 15 participants completed the 12-week study. There were no serious adverse events, no drug-related adverse events, and no choroidal neovascularization developed in either eye. Mean visual acuity and GA lesion area appeared stable through week 12 for all cohorts. Pharmacokinetic analyses indicated that NGM621 serum exposures appeared to be dose proportional, and no antidrug antibodies were identified at any of the evaluated time points.

CONCLUSIONS

In this small, open-labeled, 12-week phase 1 study, NGM621 was safe and tolerable when administered intravitreally up to 15 mg.<END ABSTRACT>

中文翻译：

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用 NGM621 抑制地理萎缩中的补体因子 3：1 期剂量递增研究结果

目的

评估单次和多次玻璃体内注射 NGM621 在地理萎缩 (GA) 患者中的安全性和耐受性，并表征药代动力学和免疫原性潜力。

设计

多中心、开放标签、单剂量和多剂量 1 期研究。

方法

在美国的 4 个地点登记了 15 名患者。参与者患有继发于年龄相关性黄斑变性的 GA，病变大小≥2.5 mm ²，研究眼睛的最佳矫正视力为 4 到 54 个字母（20/80 到 20/800 Snellen 等效值），并且两只眼睛都没有脉络膜新生血管病史。符合资格标准的患者接受单次递增剂量阶段（2 mg、7.5 mg 和 15 mg）治疗或在多剂量阶段接受 2 剂 NGM621（15 mg），间隔 4 周并监测 12 周（85天）。评估包括不良事件、最佳矫正视力、低亮度视力、生命体征、临床实验室评估、通过眼底自发荧光测量的 GA 病变面积、光谱域光学相干断层扫描以及药代动力学、免疫原性和药效学评估。

结果

所有 15 名参与者都完成了为期 12 周的研究。两只眼睛均未出现严重不良事件、药物相关不良事件和脉络膜新生血管。对于所有队列，平均视力和 GA 病变面积在第 12 周内表现稳定。药代动力学分析表明，NGM621 血清暴露似乎与剂量成正比，并且在任何评估的时间点均未发现抗药物抗体。

结论

在这项小型、开放标签、为期 12 周的 1 期研究中，NGM621 在玻璃体内给药高达 15 mg 时是安全且可耐受的。<END ABSTRACT>