Summary

In a Phase I study, the intra-articular injection of FURESTEM-OA Kit Inj., containing allogeneic umbilical cord blood-derived mesenchymal stem cells, demonstrated a favorable safety profile and significant improvements in pain and function in patients with knee osteoarthritis, particularly at middle and high doses.

Abstract

Background

Umbilical cord blood derived mesenchymal stem cells (UC-MSCs) have been utilized for the treatment of knee cartilage defects in patients with osteoarthritis. Despite their application, it has not yet been approved as disease-modifying osteoarthritis drugs (DMOADs) capable of inducing cartilage regeneration and structural modification in the treatment of OA, leaving a significant unmet need. The intra-articular injection of allogeneic UC-MSCs can be a cost-effective treatment by delivering premade UC-MSCs without the need for surgery. FURESTEM-OA Kit Inj., a combined therapy containing allogeneic UC-MSCs and cartilage acellular matrix, has demonstrated regeneration of damaged cartilage in various preclinical models. We conducted a first-in-human phase 1 trial to evaluate the safety, tolerability, and exploratory efficacy of the FURESTEM-OA Kit Inj. in patients with knee osteoarthritis.

Materials And Methods

This study followed a 3 + 3 dose escalation design with enrollment of 6 subjects in cohort 3. A total of twelve patients, diagnosed with Kellgren-Lawrence grade 2-3 osteoarthritis based on knee radiography, received a single intra-articular injection of FURESTEM-OA Kit Inj. 2.5×10^7 cells (cohort 1, low-dose, n=3), 5.0×10^7 cells (cohort 2, middle-dose, n=3) and 1.0×10^8 cells (cohort 3, high-dose, n=6). The primary endpoint was to assess dose-limiting toxicities (DLTs) and to determine the maximum tolerated dose (MTD). Secondary endpoints assessed efficacy based on changes in pain and function scoring indices over 24 weeks, using the International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Visual Analogue Scale (VAS) indices. Higher scores on the IKDC and WOMAC indicate better clinical outcomes, whereas lower score on the KOOS and VAS reflect symptom relief. Mixed-effects model with post-hoc pairwise comparisons were employed for statistical analysis.

Results

No DLT was encountered during dose escalation and the MTD was not reached. Grade 2 and above treatment-related adverse events were a moderate knee swelling (grade 2), which resolved within 6 weeks. Significant improvements in pain and function over time were observed in cohorts 2 and 3, as indicated by mixed-effect model analyses with post-hoc comparisons (p < 0.05 for all indices). At 24 weeks post-injection, cohorts 2 and 3 showed statistically significant improvements from baseline across all indices (p < 0.05), whereas cohort 1 did not. The greatest improvements at 24 weeks from baseline were generally observed in cohort 3. Specifically, IKDC scores increased by 15.2%, 89.7%, and 89.3% in cohorts 1, 2, and 3, respectively; WOMAC scores increased by 5.1%, 104.8%, and 38.9%; VAS scores decreased by 14.6%, 78.8%, and 84.8%; and pain scores in the KOOS decreased by 3.2%, 62.6%, and 64.7% and stiffness scores in the KOOS decreased by 2.2%, 72.7%, and 55.3%, respectively.

Conclusion

Intra-articular injection of FURESTEM-OA Kit Inj. was well tolerated with a favorable safety profile. The middle- and high-dose of FURESTEM-OA Kit Inj. demonstrated significant improvement in pain and function over time, which will be evaluated in phase 2 clinical trials.