同种异体脂肪间充质干细胞制剂治疗膝骨关节炎的安全性和有效性：一项I/IIa期随机对照试验。
Safety and efficacy of an allogeneic adipose-derived mesenchymal stem cell preparation in the treatment of knee osteoarthritis: A Phase I/IIa randomised controlled trial.
作者信息
Freitag Julien, Chamberlain Matthew, Wickham James, Shah Kiran, Cicuttini Flavia, Wang Yuanyuan, Solterbeck Ann
机构信息
School of Rural Medicine, Charles Sturt University, Orange, NSW, 2800, Australia.
Melbourne Stem Cell Centre Research, Box Hill, VIC, 3128, Australia.
出版信息
Osteoarthr Cartil Open. 2024 Jul 1;6(3):100500. doi: 10.1016/j.ocarto.2024.100500. eCollection 2024 Sep.
OBJECTIVES
To assess the safety and efficacy of an allogeneic adipose-derived mesenchymal stem cell preparation (MAG200) in the treatment of knee osteoarthritis over 12 months.
DESIGN
A single-centre, double-blind, ascending dose, randomised controlled trial. 40 participants with moderate knee osteoarthritis were randomised to receive a single intra-articular injection of MAG200 (dose cohorts:10, 20, 50, 100 × 10 cells) or placebo. Primary objectives were safety and efficacy according to a compound responder analysis of minimal clinically important difference in pain (numerical pain rating scale [NPRS]) and function (Knee Injury and Osteoarthritis Outcome Score - Function in Daily Living subscale [KOOS]) at month 12. Secondary efficacy outcomes included changes from baseline in patient reported outcome measures and evaluation of disease-modification using quantitative MRI.
RESULTS
Treatment was well tolerated with no treatment-related serious adverse events. MAG200 cohorts reported a greater proportion of responders than placebo and demonstrated clinical and statistically significant improvement in pain and clinically relevant improvement in all KOOS subscales. MAG200 demonstrated a reproducible treatment effect over placebo, which was clinically relevant for pain in the 10 × 10 dose cohort (mean difference NPRS:-2.25[95%CI:-4.47,-0.03, p = 0.0468]) and for function in the 20 × 10 and 100 × 10 dose cohorts (mean difference KOOS:10.12[95%CI:-1.51,21.76, p = 0.0863] and 10.81[95%CI:-1.42,23.04, p = 0.0810] respectively). A trend in disease-modification was observed with improvement in total knee cartilage volume in MAG200 10, 20, and 100 × 10 dose cohorts, with progression of osteoarthritis in placebo, though this was not statistically significant. No clear dose response was observed.
CONCLUSION
This early-phase study provides supportive safety and efficacy evidence to progress MAG200 to later-stage trial development.
TRIAL REGISTRATION
ACTRN12617001095358/ACTRN12621000622808.
目的
评估同种异体脂肪间充质干细胞制剂（MAG200）治疗膝关节骨关节炎12个月的安全性和有效性。
设计
单中心、双盲、递增剂量、随机对照试验。40名中度膝关节骨关节炎患者被随机分组，接受单次关节腔内注射MAG200（剂量组：10、20、50、100×10⁶细胞）或安慰剂。主要目标是根据12个月时疼痛（数字疼痛评分量表[NPRS]）和功能（膝关节损伤和骨关节炎疗效评分-日常生活功能亚量表[KOOS]）最小临床重要差异的复合反应者分析来评估安全性和有效性。次要疗效指标包括患者报告结局指标相对于基线的变化，以及使用定量MRI评估疾病修饰情况。
结果
治疗耐受性良好，未发生与治疗相关的严重不良事件。与安慰剂相比，MAG200剂量组报告的反应者比例更高，在疼痛方面显示出临床和统计学上的显著改善，在所有KOOS亚量表中均有临床相关改善。与安慰剂相比，MAG200显示出可重复的治疗效果，这在10×10⁶剂量组的疼痛方面具有临床相关性（平均差异NPRS：-2.25[95%CI：-4.47，-0.03，p = 0.0468]），在20×10⁶和100×10⁶剂量组的功能方面具有临床相关性（平均差异KOOS：分别为10.12[95%CI：-1.51，21.76，p = 0.0863]和10.81[95%CI：-1.42，23.04，p = 0.0810]）。在MAG200 10、20和100×10⁶剂量组中观察到疾病修饰的趋势是全膝关节软骨体积增加，而安慰剂组骨关节炎进展，尽管这在统计学上不显著。未观察到明确的剂量反应。
结论
这项早期研究为MAG200进入后期试验开发提供了支持性的安全性和有效性证据。
试验注册号
ACTRN12617001095358/ACTRN12621000622808。
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