Julien Freitag , Matthew Chamberlain , James Wickham , Kiran Shah , Flavia Cicuttini , Yuanyuan Wang , Ann Solterbeck
{"title":"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：I/IIa 期随机对照试验。","authors":"Julien Freitag , Matthew Chamberlain , James Wickham , Kiran Shah , Flavia Cicuttini , Yuanyuan Wang , Ann Solterbeck","doi":"10.1016/j.ocarto.2024.100500","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><p>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.</p></div><div><h3>Design</h3><p>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<sup>6</sup> 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<sub>ADL</sub>]) at month 12. Secondary efficacy outcomes included changes from baseline in patient reported outcome measures and evaluation of disease-modification using quantitative MRI.</p></div><div><h3>Results</h3><p>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<sup>6</sup> dose cohort (mean difference NPRS:-2.25[95%CI:-4.47,-0.03, p = 0.0468]) and for function in the 20 × 10<sup>6</sup> and 100 × 10<sup>6</sup> dose cohorts (mean difference KOOS<sub>ADL</sub>: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<sup>6</sup> dose cohorts, with progression of osteoarthritis in placebo, though this was not statistically significant. No clear dose response was observed.</p></div><div><h3>Conclusion</h3><p>This early-phase study provides supportive safety and efficacy evidence to progress MAG200 to later-stage trial development.</p></div><div><h3>Trial registration</h3><p>ACTRN12617001095358/ACTRN12621000622808.</p></div>","PeriodicalId":74377,"journal":{"name":"Osteoarthritis and cartilage open","volume":"6 3","pages":"Article 100500"},"PeriodicalIF":0.0000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665913124000670/pdfft?md5=1c90eff7a605bb0d4e7ab9178e7671fa&pid=1-s2.0-S2665913124000670-main.pdf","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"Julien Freitag , Matthew Chamberlain , James Wickham , Kiran Shah , Flavia Cicuttini , Yuanyuan Wang , Ann Solterbeck\",\"doi\":\"10.1016/j.ocarto.2024.100500\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objectives</h3><p>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.</p></div><div><h3>Design</h3><p>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<sup>6</sup> 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<sub>ADL</sub>]) at month 12. Secondary efficacy outcomes included changes from baseline in patient reported outcome measures and evaluation of disease-modification using quantitative MRI.</p></div><div><h3>Results</h3><p>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<sup>6</sup> dose cohort (mean difference NPRS:-2.25[95%CI:-4.47,-0.03, p = 0.0468]) and for function in the 20 × 10<sup>6</sup> and 100 × 10<sup>6</sup> dose cohorts (mean difference KOOS<sub>ADL</sub>: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<sup>6</sup> dose cohorts, with progression of osteoarthritis in placebo, though this was not statistically significant. No clear dose response was observed.</p></div><div><h3>Conclusion</h3><p>This early-phase study provides supportive safety and efficacy evidence to progress MAG200 to later-stage trial development.</p></div><div><h3>Trial registration</h3><p>ACTRN12617001095358/ACTRN12621000622808.</p></div>\",\"PeriodicalId\":74377,\"journal\":{\"name\":\"Osteoarthritis and cartilage open\",\"volume\":\"6 3\",\"pages\":\"Article 100500\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2665913124000670/pdfft?md5=1c90eff7a605bb0d4e7ab9178e7671fa&pid=1-s2.0-S2665913124000670-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Osteoarthritis and cartilage open\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2665913124000670\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Osteoarthritis and cartilage open","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2665913124000670","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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
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 × 106 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]) 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 × 106 dose cohort (mean difference NPRS:-2.25[95%CI:-4.47,-0.03, p = 0.0468]) and for function in the 20 × 106 and 100 × 106 dose cohorts (mean difference KOOSADL: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 × 106 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.
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