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
Abstract
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 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 [KOOS 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 × 10 6 dose cohort (mean difference NPRS:-2.25[95%CI:-4.47,-0.03, p = 0.0468]) and for function in the 20 × 10 6 and 100 × 10 6 dose cohorts (mean difference KOOS 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 × 10 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.