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.