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Abstract：
BACKGROUND: Cenegermin is approved for treatment of neurotrophic keratopathy (NK) and has been studied in patients with stage 2 or 3 NK. This study evaluated the efficacy and safety of cenegermin in adults with stage 1 NK.
METHODS: This was a phase IV, multicenter, prospective, open-label, uncontrolled trial. Adults with stage 1 NK (Mackie criteria) and decreased corneal sensitivity (≤ 4 cm) received 1 drop of cenegermin 20 mcg/ml in the affected eye(s) 6 times/day for 8 weeks with a 24-week follow-up.
RESULTS: Of 37 patients, corneal epithelial healing was observed in 84.8% (95% confidence interval [CI] 68.1-94.9%; P < 0.001) at week 8; 95.2% (95% CI 76.2-99.9%; P < 0.001) of those patients remained healed at the end of the 24-week follow-up (week 32). At week 8, 91.2% (95% CI 76.3-98.1%; P < 0.001) of patients experienced improved corneal sensitivity; this improvement was observed in 82.1% (95% CI 63.1-93.9%; P < 0.001) of patients at week 32. Mean best-corrected distance visual acuity change from baseline at week 8 was - 0.10 logMAR (standard deviation [SD], 0.15; 95% CI - 0.16 to - 0.05; P < 0.001) and at week 32 was - 0.05 logMAR (SD, 0.16; 95% CI - 0.11 to 0.01; P = 0.122). At weeks 8 and 32, 15.2% (95% CI 5.1-31.9%; P < 0.001) and 10.7% (95% CI 2.3-28.2%; P < 0.001) of patients, respectively, had a 15-letter gain from baseline. At least one adverse event (AE) was reported by 73.0% and 45.7% of patients during the treatment and follow-up periods, respectively. The most common treatment-related, treatment-emergent AEs were eye pain (37.8%), blurred vision (10.8%), and eyelid pain (8.1%); these were mostly mild or moderate and were only reported during the treatment period.
CONCLUSIONS: These results support the potential use of cenegermin for treating patients with stage 1 NK, and future confirmatory studies would be beneficial to elaborate on these findings.
BACKGROUND: DEFENDO; NCT04485546.
METHODS: This was a phase IV, multicenter, prospective, open-label, uncontrolled trial. Adults with stage 1 NK (Mackie criteria) and decreased corneal sensitivity (≤ 4 cm) received 1 drop of cenegermin 20 mcg/ml in the affected eye(s) 6 times/day for 8 weeks with a 24-week follow-up.
RESULTS: Of 37 patients, corneal epithelial healing was observed in 84.8% (95% confidence interval [CI] 68.1-94.9%; P < 0.001) at week 8; 95.2% (95% CI 76.2-99.9%; P < 0.001) of those patients remained healed at the end of the 24-week follow-up (week 32). At week 8, 91.2% (95% CI 76.3-98.1%; P < 0.001) of patients experienced improved corneal sensitivity; this improvement was observed in 82.1% (95% CI 63.1-93.9%; P < 0.001) of patients at week 32. Mean best-corrected distance visual acuity change from baseline at week 8 was - 0.10 logMAR (standard deviation [SD], 0.15; 95% CI - 0.16 to - 0.05; P < 0.001) and at week 32 was - 0.05 logMAR (SD, 0.16; 95% CI - 0.11 to 0.01; P = 0.122). At weeks 8 and 32, 15.2% (95% CI 5.1-31.9%; P < 0.001) and 10.7% (95% CI 2.3-28.2%; P < 0.001) of patients, respectively, had a 15-letter gain from baseline. At least one adverse event (AE) was reported by 73.0% and 45.7% of patients during the treatment and follow-up periods, respectively. The most common treatment-related, treatment-emergent AEs were eye pain (37.8%), blurred vision (10.8%), and eyelid pain (8.1%); these were mostly mild or moderate and were only reported during the treatment period.
CONCLUSIONS: These results support the potential use of cenegermin for treating patients with stage 1 NK, and future confirmatory studies would be beneficial to elaborate on these findings.
BACKGROUND: DEFENDO; NCT04485546.
摘要：
背景：Cenegermin已被批准用于治疗神经营养性角膜病变（NK），并已在2或3期NK患者中进行了研究。这项研究评估了cenegermin在1期NK成人中的疗效和安全性。
方法：这是第四阶段，多中心，prospective,开放标签，不受控制的审判。患有1期NK（Mackie标准）和角膜敏感性降低（≤4cm）的成年人在受影响的眼睛中接受1滴cenegermin20mcg/ml，每天6次，共8周，并进行24周的随访。
结果：在37例患者中，在第8周,观察到84.8%(95%置信区间[CI]68.1~94.9%;P<0.001)的角膜上皮愈合;在24周随访结束时(第32周),这些患者中有95.2%(95%CI76.2~99.9%;P<0.001)仍愈合.在第8周，91.2%（95%CI76.3-98.1%；P<0.001）的患者角膜敏感性改善；在第32周，82.1%（95%CI63.1-93.9%；P<0.001）的患者观察到这种改善。在第8周时，与基线相比的平均最佳校正距离视力变化为-0.10logMAR（标准偏差[SD]，0.15；95%CI-0.16至-0.05；P<0.001），第32周为-0.05logMAR（SD，0.16；95%CI-0.11至0.01；P=0.122）。在第8周和第32周，15.2%（95%CI5.1-31.9%；P<0.001）和10.7%（95%CI2.3-28.2%；P<0.001）的患者，分别,从基线增加了15个字母。在治疗和随访期间，73.0%和45.7%的患者至少报告了一次不良事件(AE)。分别。最常见的治疗相关，治疗中出现的不良事件是眼痛（37.8%），视力模糊(10.8%),和眼睑疼痛（8.1％）；这些大多是轻度或中度，仅在治疗期间报告。
结论：这些结果支持cenegermin用于治疗1期NK患者的潜在用途。未来的验证性研究将有助于详细阐述这些发现。
背景：DEFENDO;NCT04485546。
方法：这是第四阶段，多中心，prospective,开放标签，不受控制的审判。患有1期NK（Mackie标准）和角膜敏感性降低（≤4cm）的成年人在受影响的眼睛中接受1滴cenegermin20mcg/ml，每天6次，共8周，并进行24周的随访。
结果：在37例患者中，在第8周,观察到84.8%(95%置信区间[CI]68.1~94.9%;P<0.001)的角膜上皮愈合;在24周随访结束时(第32周),这些患者中有95.2%(95%CI76.2~99.9%;P<0.001)仍愈合.在第8周，91.2%（95%CI76.3-98.1%；P<0.001）的患者角膜敏感性改善；在第32周，82.1%（95%CI63.1-93.9%；P<0.001）的患者观察到这种改善。在第8周时，与基线相比的平均最佳校正距离视力变化为-0.10logMAR（标准偏差[SD]，0.15；95%CI-0.16至-0.05；P<0.001），第32周为-0.05logMAR（SD，0.16；95%CI-0.11至0.01；P=0.122）。在第8周和第32周，15.2%（95%CI5.1-31.9%；P<0.001）和10.7%（95%CI2.3-28.2%；P<0.001）的患者，分别,从基线增加了15个字母。在治疗和随访期间，73.0%和45.7%的患者至少报告了一次不良事件(AE)。分别。最常见的治疗相关，治疗中出现的不良事件是眼痛（37.8%），视力模糊(10.8%),和眼睑疼痛（8.1％）；这些大多是轻度或中度，仅在治疗期间报告。
结论：这些结果支持cenegermin用于治疗1期NK患者的潜在用途。未来的验证性研究将有助于详细阐述这些发现。
背景：DEFENDO;NCT04485546。
