Osteoarthritis and Cartilage Open (Sep 2024)

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

  • Julien Freitag,
  • Matthew Chamberlain,
  • James Wickham,
  • Kiran Shah,
  • Flavia Cicuttini,
  • Yuanyuan Wang,
  • Ann Solterbeck,
  • Lucinda Kenihan,
  • Lesley-Anne Kelly,
  • Renee Castelluccio,
  • Ellee Picken,
  • Melissa Grogan,
  • Michael Kenihan,
  • Abi Tenen,
  • Nirali Shah,
  • Carla Lutz,
  • Teena George,
  • Iresha Wickramasinghe

Journal volume & issue
Vol. 6, no. 3
p. 100500

Abstract

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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. Trial registration: ACTRN12617001095358/ACTRN12621000622808.

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