Safety and Efficacy of Allogeneic Integrin α10β1-Selected Mesenchymal Stem Cells in the Treatment of Knee Osteoarthritis: A First-In-Human Phase I/IIa Dose Escalation Study.

PurposeSafety and efficacy of allogeneic integrin α10β1-selected MSCs (integrin α10-MSCs) have been shown in two post-traumatic osteoarthritis (OA) equine models. The aim of this study is to evaluate safety, tolerability and preliminary efficacy of allogeneic integrin α10-MSCs in human symptomatic knee OA.MethodsIn a first-in-human prospective multicentre phase I/IIa dose escalation study, 24 patients (41-75 years, Kellgren-Lawrence grade II-III knee OA) were treated with a single intra-articular injection of 4, 8 or 16 million integrin α10-MSCs. Safety and tolerability were assessed by adverse events, electrocardiography, vital signs, and physical and laboratory examinations. Clinical outcome was measured by visual analogue scale (VAS) for pain and Knee injury and Osteoarthritis Outcome Score (KOOS). Structural outcomes were assessed by X-ray and MRI. The total follow-up period was 24 months for the highest dose and 18 months for the lower doses.ResultsThe most frequently reported study drug-related adverse events were injection site pain, joint swelling and injection site movement impairment. All doses showed sustained improvements in pain and function, whereas the 16 million dose cohort showed earlier effects. The 16 million dose cohort also showed a reduction in bone marrow lesions, signs of an improved cartilage quality by T2* relaxation time, and a stable medial minimum joint space width.ConclusionsThis study demonstrated safety and efficacy of intra-articular injection of integrin α10-MSCs for the treatment of mild to moderate knee OA. At a dose of 16 million integrin α10-MSCs, a potentially quick and long-lasting therapeutic effect, supportive of disease-modification, was evident.