Öhnstedt Emelie, Vågesjö Evelina, Fasth Andreas, Lofton Tomenius Hava, Dahg Pia, Jönsson Sofia, Tyagi Nisha, Åström Mikael, Myktybekova Zhanar, Ringstad Lovisa, Jorvid Margareth, Frank Peter, Hedén Per, Roos Stefan, Phillipson Mia
Ilya Pharma AB, Dag Hammarskjölds Väg 30, 752 37 Uppsala, Sweden.
Uppsala University, Department of Medical Cell Biology, 751 23 Uppsala, Sweden.
EClinicalMedicine. 2023 May 25;60:102014. doi: 10.1016/j.eclinm.2023.102014. eCollection 2023 Jun.
Impaired wound healing is a growing medical problem and very few approved drugs with documented clinical efficacy are available. CXCL12-expressing lactic acid bacteria, (ILP100-Topical), has been demonstrated to accelerate wound healing in controlled preclinical models. In this first-in-human study, the primary objective was to determine safety and tolerability of the drug candidate ILP100-Topical, while secondary objectives included assessments of clinical and biologic effects on wound healing by traditionally accepted methods and explorative and traceable assessments.
SITU-SAFE is an adaptive, randomised, double-blind, placebo-controlled, first-in-human phase 1 trial (EudraCT 2019-000680-24) consisting of a single (SAD) and a multiple ascending dose (MAD) part of three dose cohorts each. The study was performed at the Phase 1 Unit, Uppsala University Hospital, Uppsala, Sweden. Data in this article were collected between Sep 20th, 2019 and Oct 20th 2021. In total 240 wounds were induced on the upper arms in 36 healthy volunteers. SAD: 12 participants, 4 wounds (2/arm), MAD: 24 participants, 8 wounds (4/arm). Wounds in each participant were randomised to treatment with placebo/saline or ILP100-Topical.
In all individuals and doses, ILP100-Topical was safe and well-tolerated with no systemic exposure. A combined cohort analysis showed a significantly larger proportion of healed wounds (p = 0.020) on Day 32 by multi-dosing of ILP100-Topical when compared to saline/placebo (76% (73/96) and 59% (57/96) healed wounds, respectively). In addition, time to first registered healing was shortened by 6 days on average, and by 10 days at highest dose. ILP100-Topical increased the density of CXCL12 cells in the wounds and local wound blood perfusion.
The favourable safety profile and observed effects on wound healing support continued clinical development of ILP100-Topical for the treatment of complicated wounds in patients.
Ilya Pharma AB (Sponsor), H2020 SME Instrument Phase II (#804438), Knut and Alice Wallenberg foundation.
伤口愈合受损是一个日益严重的医学问题，目前可用的经临床疗效证实的获批药物极少。表达CXCL12的乳酸菌（ILP100-局部用）已在对照临床前模型中被证明可加速伤口愈合。在这项首次人体研究中，主要目标是确定候选药物ILP100-局部用的安全性和耐受性，次要目标包括通过传统公认方法评估对伤口愈合的临床和生物学影响以及探索性和可追溯性评估。
SITU-SAFE是一项适应性、随机、双盲、安慰剂对照的首次人体1期试验（欧洲临床试验注册号2019-000680-24），包括单剂量（SAD）和多剂量递增（MAD）两部分，各有三个剂量组。该研究在瑞典乌普萨拉大学医院的1期病房进行。本文中的数据收集于2019年9月20日至2021年10月20日之间。共在36名健康志愿者的上臂诱导出240处伤口。SAD组：12名参与者，4处伤口（每只手臂2处）；MAD组：24名参与者，8处伤口（每只手臂4处）。将每位参与者的伤口随机分配接受安慰剂/生理盐水或ILP100-局部用治疗。
在所有个体和剂量中，ILP100-局部用均安全且耐受性良好，无全身暴露。一项合并队列分析显示，与生理盐水/安慰剂相比，在第32天时，多剂量使用ILP100-局部用治疗的愈合伤口比例显著更高（p = 0.020）（分别为76%（73/96）和59%（57/96）的伤口愈合）。此外，首次记录到愈合的时间平均缩短了6天，最高剂量时缩短了10天。ILP100-局部用增加了伤口中CXCL12细胞的密度和局部伤口血液灌注。
良好的安全性和观察到的对伤口愈合的影响支持ILP100-局部用继续用于患者复杂伤口治疗的临床开发。
伊利亚制药公司（赞助商）、H2020中小企业仪器二期（项目编号804438）、克努特和爱丽丝·瓦伦堡基金会。
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