间充质干细胞分泌组疗法（KPI-012）治疗持续性角膜上皮缺陷的安全性和有效性：1b期试验

IF 1.5 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental Pub Date : 2025-01-01 DOI:10.1016/j.curtheres.2025.100799

Valeria Sánchez Huerta MD , Hugo Quiroz-Mercado MD , Enrique O. Graue-Hernández MD, MSc , Alejandro Navas MD, MSc , Spencer Alford PhD , Darius Kharabi JD, MBA , Stephen Pflugfelder MD

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引用次数: 0

摘要

背景：持续性角膜上皮缺损（PCED）是一种常规治疗难以治愈的疾病。KPI-012是一种局部间充质干细胞分泌组疗法，正在研究用于PCED治疗。目的在一项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、耐受性和角膜创面愈合效果。方法：首先在一个预先存在永久性视力丧失且无活动性角膜疾病（ = 3）的参与者的初始安全性队列中评估局部自我给药KPI-012治疗（每天两次，持续1周）的安全性和耐受性。然后在几种病因的PCED患者（n = 9）中评估KPI-012的安全性和有效性，这些患者每天两次自我服用KPI-012，持续4周，其中一名参与者自我服用8周（疗效队列）。结果skpi -012在安全性和有效性队列中均具有良好的耐受性。在疗效队列中（n = 9），8名参与者中有6名（75%）在治疗期间表现出病变完全愈合，8名参与者中有4名（50%）在开始KPI-012治疗后1周内实现完全愈合（非治疗相关不良事件意味着1名参与者被研究者撤回）。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pced相关眼部疼痛的患者中（n = 7），所有参与者的疼痛水平在1周后下降，3周后，没有参与者报告眼部疼痛。这项小型1b期开放标签试验的结果表明，对于多种病因的PCED患者，每天两次的KPI-012治疗显示出良好的安全性和有效性，并可能促进伤口快速愈合。小样本量限制了研究结果的普遍性，因此需要更大样本量的后期临床研究来确定统计学驱动的治疗效果。

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Safety and Efficacy of a Mesenchymal Stem Cell Secretome Therapy (KPI-012) for Persistent Corneal Epithelial Defects: A Phase 1b Trial

Background

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.

Objective

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.

Methods

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).

Results

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.

Conclusions

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.

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来源期刊

Current Therapeutic Research-clinical and Experimental 医学-药学

CiteScore

3.50

自引率

0.00%

发文量

审稿时长

3 months

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