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

被引:1
作者
Freitag, Julien [1 ,2 ,3 ]
Chamberlain, Matthew [2 ]
Wickham, James [4 ]
Shah, Kiran [3 ]
Cicuttini, Flavia [5 ,6 ]
Wang, Yuanyuan [5 ]
Solterbeck, Ann [7 ]
机构
[1] Charles Sturt Univ, Sch Rural Med, Orange, NSW 2800, Australia
[2] Melbourne Stem Cell Ctr Res, Box Hill, Vic 3128, Australia
[3] Magellan Stem Cells, 9A Sugar Gum Court, Braeside, Vic 3195, Australia
[4] Charles Sturt Univ, Sch Dent & Med Sci, Orange, NSW 2800, Australia
[5] Monash Univ, Sch Publ Hlth & Prevent Med, Melbourne, Vic 3004, Australia
[6] Alfred Hosp, Dept Rheumatol, Melbourne, Vic 3004, Australia
[7] Stat Revelat Pty Ltd, Ocean Grove, Vic 3226, Australia
来源
OSTEOARTHRITIS AND CARTILAGE OPEN | 2024年 / 6卷 / 03期
关键词
Osteoarthritis; Knee; Mesenchymal stem cells; Allogeneic; Cartilage; Intra-articular; Disease modification; Regenerative medicine; STROMAL CELLS; ARTHROPLASTY; THERAPY; PAIN;
D O I
10.1016/j.ocarto.2024.100500
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
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 x 106 6 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 [KOOSADL]) ADL ]) 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 x 106 6 dose cohort (mean difference NPRS:-2.25[95%CI:-4.47,-0.03, p = 0.0468]) and for function in the 20 x 106 6 and 100 x 106 6 dose cohorts (mean difference KOOSADL:10.12[95%CI:-1.51,21.76, ADL :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 x 106 6 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.
引用
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页数:12
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