评价局部应用重组人神经生长因子(cenegermin)治疗神经营养性角膜病变的疗效和安全性。
多中心,随机化,双面蒙面,车辆控制试验。
伴有或不伴有基质变薄的神经营养性持续性上皮缺损患者。
NGF0214试验,在美国的11个地点进行,随机将48例患者1:1服用cenegermin20μg/ml或载体滴眼液,每天6滴,为期8周的掩蔽治疗。随访24周。在接受研究药物的所有患者中评估安全性。通过意向治疗评估疗效。
主要终点是8周掩蔽治疗后神经营养性损伤(持续性上皮缺损或角膜溃疡)的愈合。蒙面的中央阅读器在随机临床图片中测量了神经营养性病变,然后评估愈合状态常规(<0.5mm荧光染色在病变区域的最大尺寸)和保守(0-mm病变染色和没有其他残留染色)。次要变量包括掩蔽治疗4周时的角膜愈合(关键次要终点),病变大小的整体变化,疾病进展率,以及从基线到第8周视力和角膜敏感度的变化。
角膜愈合的常规评估在第8周时显示出统计学上的显着差异:与24例接受赋形剂治疗的患者中的7例(29.2%)相比,23例接受cenegermin治疗的患者中有16例(69.6%)的病变染色小于0.5mm(40.4%;95%置信区间[CI],14.2%-66.6%;P=0.006)。角膜愈合的保守评估在第8周也达到了统计学意义:与24例接受赋形剂治疗的患者中的4例(16.7%)相比,23例接受cenegermin治疗的患者中有15例(65.2%)达到了0mm的病变染色,没有其他残留染色(48.6%;95%CI,24.0%-73.1%;P<0.001)。此外,角膜愈合的保守测量在第4周(关键次要终点)显示有统计学意义.与车辆相比,接受cenegermin治疗的患者在掩盖治疗期间,病变大小和疾病进展率在统计学上显着降低。Cenegermin耐受性良好;不良反应主要是局部的,温和,和短暂的。
Cenegermin治疗在与未愈合角膜缺损相关的神经营养性角膜病变中显示出比媒介物更高的角膜愈合率。
To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with neurotrophic keratopathy.
Multicenter, randomized, double-masked, vehicle-controlled
trial.
Patients with neurotrophic persistent epithelial defect with or without stromal thinning.
The NGF0214
trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 μg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received
study drug. Efficacy was assessed by intention to treat.
The primary end point was healing of the neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally (<0.5 mm of fluorescein staining in the greatest dimension of the lesion area) and conservatively (0-mm lesion staining and no other residual staining). Secondary variables included corneal healing at 4 weeks of masked treatment (key secondary end point), overall changes in lesion size, rates of disease progression, and changes in visual acuity and corneal sensitivity from baseline to week 8.
Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2%), 16 of 23 cenegermin-treated patients (69.6%) achieved less than 0.5 mm of lesion staining (+40.4%; 95% confidence interval [CI], 14.2%-66.6%; P = 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7%), 15 of 23 cenegermin-treated patients (65.2%) achieved 0 mm of lesion staining and no other residual staining (+48.6%; 95% CI, 24.0%-73.1%; P < 0.001). Moreover, the conservative measure of corneal healing showed statistical significance at week 4 (key secondary end point). Compared to vehicle, cenegermin-treated patients showed statistically significant reductions in lesion size and disease progression rates during masked treatment. Cenegermin was well tolerated; adverse effects were mostly local, mild, and transient.
Cenegermin treatment showed higher rates of corneal healing than vehicle in neurotrophic keratopathy associated with nonhealing corneal defects.