Huerta Valeria Sánchez, Quiroz-Mercado Hugo, Graue-Hernández Enrique O, Navas Alejandro, Alford Spencer, Kharabi Darius, Pflugfelder Stephen
APEC Hospital de la Ceguera, Mexico City, Mexico.
Instituto de Oftalmología Fundación Conde de Valenciana, Mexico City, Mexico.
Curr Ther Res Clin Exp. 2025 May 15;103:100799. doi: 10.1016/j.curtheres.2025.100799. eCollection 2025.
Persistent corneal epithelial defect (PCED) is a condition often refractory to conventional treatments. KPI-012 is a topical mesenchymal stem cell secretome therapy under investigation for PCED management.
To assess the safety, tolerability, and corneal wound healing efficacy of KPI-012 in a phase 1b, proof-of-concept, open-label, single-arm clinical trial.
The safety profile and tolerability of topical self-administered KPI-012 therapy (twice daily, 1-week duration) were first evaluated in an initial safety cohort of participants with pre-existing permanent vision loss and no active corneal disease (n = 3). The safety profile and efficacy of KPI-012 were then assessed in participants with PCED of several etiologies (n = 9), who self-administered KPI-012 twice daily for up to 4 weeks with one participant self-administering for 8 weeks (efficacy cohort).
KPI-012 was well tolerated in both the safety profile and efficacy cohorts. In the efficacy cohort (n = 9), 6 of 8 participants (75%) demonstrated complete healing of the lesion during the treatment period, with 4 of 8 (50%) achieving complete healing within 1 week of commencing KPI-012 therapy (a nontreatment-related adverse event meant 1 participant was withdrawn by the investigator). KPI-012 was well tolerated, with only 1 participant experiencing treatment-related adverse events. In patients who reported PCED-related ocular pain at baseline (n = 7), pain levels decreased in all participants after 1 week, and after 3 weeks, no participant reported ocular pain.
The results from this small phase 1b open-label trial suggest that in participants with PCED of multiple etiologic origin, twice daily KPI-012 therapy exhibits a favorable safety profile-efficacy profile and may promote rapid wound healing. The small sample size limits the generalizability of the findings, and thus a later-phase clinical investigation with a larger sample size is warranted to establish the statistically driven therapeutic effect.
持续性角膜上皮缺损（PCED）是一种常对传统治疗有抵抗性的病症。KPI-012是一种正在研究用于治疗PCED的局部间充质干细胞分泌组疗法。
在一项1b期概念验证、开放标签、单臂临床试验中评估KPI-012的安全性、耐受性和角膜伤口愈合疗效。
首先在初始安全性队列中评估局部自我给药的KPI-012疗法（每日两次，持续1周）的安全性和耐受性，该队列中的参与者已有永久性视力丧失且无活动性角膜疾病（n = 3）。然后在患有多种病因的PCED的参与者中评估KPI-012的安全性和疗效（n = 9），这些参与者每日两次自我给药KPI-012，最长4周，其中一名参与者自我给药达8周（疗效队列）。
KPI-012在安全性队列和疗效队列中耐受性均良好。在疗效队列（n = 9）中，8名参与者中有6名（75%）在治疗期间病变完全愈合，8名中有4名（50%）在开始KPI-012治疗后1周内实现完全愈合（1名参与者因与治疗无关的不良事件被研究者撤组）。KPI-012耐受性良好，只有1名参与者出现与治疗相关的不良事件。在基线时报告有PCED相关眼痛的患者（n = 7）中，所有参与者在1周后疼痛水平降低，3周后，无参与者报告眼痛。
这项小型1b期开放标签试验的结果表明，在患有多种病因的PCED的参与者中，每日两次的KPI-012疗法显示出良好的安全性-疗效概况，且可能促进伤口快速愈合。样本量小限制了研究结果的普遍性，因此有必要进行更大样本量的后期临床研究以确定统计学驱动的治疗效果。
