近日，美国斯坦福大学医学院Amanda J Moore团队研究了Prademagene zamikeracel治疗隐性营养不良性大疱性表皮松解症伤口的疗效与安全性。2025年6月23日出版的《柳叶刀》杂志发表了这项最新研究成果。

隐性营养不良大疱性表皮松解症（RDEB）是一种罕见的遗传性皮肤病，由编码VII型胶原蛋白的COL7A1基因突变引起。患有RDEB的人皮肤脆弱，大多数人会有较大的慢性伤口。该研究旨在评估一次性手术应用prademagene zamikeracel在伤口愈合中的疗效和安全性。

这项随机、开放标签、患者内部对照的3期试验在美国的两家机构进行。符合条件的患者年龄在6岁或以上，临床和遗传学诊断为RDEB，至少有两个慢性伤口（20 cm²），对VII型胶原没有免疫反应的证据，表达VII型胶原的氨基端NC1片段。受试者的大型慢性伤口按大小、慢性程度和解剖区域成对匹配，并计算机随机（1:1）分配到治疗组（prademagene zamikeracel）或对照组（标准护理组）。没有双盲。Prademagene zamikeracel是一种自体COL7A1基因修饰的细胞片，用于缝合在大的慢性RDEB伤口上。每名患者最多可治疗6处伤口。主要终点是在所有患者及其随机伤口的意向治疗人群中，伤口在第24周愈合和疼痛从基线减少至少50%的比例。安全性分析人群包括所有患者并评估伤口，随机和非随机。

在2020年1月1日至2022年3月31日期间，研究组筛选了15名患者，纳入了11名患者（43对随机伤口）。11名参与者中有4名（36%）是男性，7名（64%）是女性，中位年龄为21岁（IQR 17-30）。86例伤口匹配并随机分组：43例（50%）为prademagene zamikeracel组，43例（50%）为对照组。在第24周，治疗的43个伤口中有35个（81%）比基线愈合至少50%，而对照组的43个伤口中有7个（16%）愈合(平均差异67%)。从基线到第24周，伤口疼痛的平均变化为-3.07，对照组为-0.90（平均两两差异为-2/23[-3·45至-0·66]；p = 0·0002）。未观察到严重的治疗相关不良事件。

研究结果表明，与对照组相比，Prademagene zamikeracel改善了伤口愈合和疼痛，并且耐受性良好，支持其减轻大型慢性RDEB伤口患者伤口负担的潜力。

附：英文原文

Title: Prademagene zamikeracel for recessive dystrophic epidermolysis bullosa wounds (VIITAL): a two-centre, randomised, open-label, intrapatient-controlled phase 3 trial

Author: Jean Y Tang, M Peter Marinkovich, Karen Wiss, Daniel McCarthy, Amanda Truesdale, Albert S Chiou, Edward Eid, Joyce K McIntyre, Irene Bailey, Louise K Furukawa, Emily S Gorell, Nicki Harris, Rohit K Khosla, H Peter Lorenz, Ying Lu, Jaron Nazaroff, I Dmitriy Grachev, Amanda J Moore

Issue&Volume: 2025-06-23

Abstract:

Background

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin disease caused by mutations in the COL7A1 gene encoding type VII collagen. Individuals with RDEB have fragile skin and most develop large, chronic wounds. The aim of the VIITAL study was to evaluate the efficacy and safety of a one-time surgical application of prademagene zamikeracel in wound healing.

Methods

This randomised, open-label, intrapatient-controlled, phase 3 trial was conducted at two institutions in the USA. Eligible patients were aged 6 years or older, had a confirmed clinical and genetic diagnosis of RDEB, at least two chronic wounds (>20 cm2), had no evidence of an immune response to type VII collagen, and expressed the amino-terminal NC1 fragment of type VII collagen. Large, chronic wounds on the participants were matched in pairs by size, chronicity, and anatomical region and computer randomised (1:1) to treatment (prademagene zamikeracel) or control (standard of care). There was no masking. Prademagene zamikeracel is an autologous COL7A1 gene-modified cellular sheet that is sutured onto to a large, chronic RDEB wound. A maximum of six wounds could be treated with prademagene zamikeracel per patient. The coprimary endpoints were the proportion of wounds with at least 50% healing and pain reduction from baseline at week 24 in the intention-to-treat population of all patients and their randomised wounds. The safety analysis population included all patients and evaluated wounds, randomised and non-randomised. This completed trial was registered with ClinicalTrials.gov (NCT04227106).

Findings

Between Jan 1, 2020, and March 31, 2022, 15 patients were screened and 11 were enrolled (43 randomised wound pairs). Four (36%) of 11 participants were male and seven (64%) of 11 participants were female, with a median age of 21 years (IQR 17–30). 86 wounds were matched and randomised: 43 (50%) to prademagene zamikeracel and 43 (50%) to control. At week 24, 35 (81%) of 43 treated wounds were at least 50% healed from baseline for prademagene zamikeracel compared with seven (16%) of 43 control wounds (mean difference 67% [95% CI 50 to 89]; p<0·0001). The mean change from baseline to week 24 in wound pain was –3·07 with prademagene zamikeracel and –0·90 in controls (mean pairwise difference –2·23 [–3·45 to –0·66]; p=0·0002). No serious treatment-related adverse events were observed.

Interpretation

Prademagene zamikeracel improved wound healing and pain versus control and was well tolerated, supporting its potential to reduce wound burden in patients with large, chronic RDEB wounds.

DOI: 10.1016/S0140-6736(25)00778-0

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00778-0/abstract