TY - JOUR
T1 - Safety and efficacy of an allogeneic adipose-derived mesenchymal stem cell preparation in the treatment of knee osteoarthritis
T2 - A phase I/IIa randomised controlled trial
AU - Melbourne Stem Cell Centre Research Group
AU - Magellan Stem Cells Group
AU - Freitag, Julien
AU - Chamberlain, Matthew
AU - Wickham, James
AU - Shah, Kiran
AU - Cicuttini, Flavia
AU - Wang, Yuanyuan
AU - Solterbeck, Ann
AU - Kenihan, Lucinda
AU - Kelly, Lesley Anne
AU - Castelluccio, Renee
AU - Picken, Ellee
AU - Grogan, Melissa
AU - Kenihan, Michael
AU - Tenen, Abi
AU - Shah, Nirali
AU - Lutz, Carla
AU - George, Teena
AU - Wickramasinghe, Iresha
N1 - Publisher Copyright:
© 2024 Magellan Stem Cells
PY - 2024/9
Y1 - 2024/9
N2 - 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.
AB - 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.
KW - Allogeneic
KW - Cartilage
KW - Disease modification
KW - Intra-articular
KW - Knee
KW - Mesenchymal stem cells
KW - Osteoarthritis
KW - Regenerative medicine
UR - https://www.scopus.com/pages/publications/85199460865
UR - https://www.scopus.com/pages/publications/85199460865#tab=citedBy
U2 - 10.1016/j.ocarto.2024.100500
DO - 10.1016/j.ocarto.2024.100500
M3 - Article
C2 - 39161739
AN - SCOPUS:85199460865
SN - 2665-9131
VL - 6
SP - 1
EP - 12
JO - Osteoarthritis and Cartilage Open
JF - Osteoarthritis and Cartilage Open
IS - 3
M1 - 100500
ER -