Safety and Tolerability of Intra-Articular Injection of Adipose-Derived Mesenchymal Stem Cells GXCPC1 in 11 Subjects With Knee Osteoarthritis: A Nonrandomized Pilot Study Without a Control Arm

Abstract

The current study aimed to determine the safety profile of intra-articular-injected allogeneic adipose-derived mesenchymal stem cells (ADSCs) GXCPC1 in subjects with knee osteoarthritis (OA) and its preliminary efficacy outcome. The 3 + 3 phase I study was designed with two dose-escalation cohorts: low dose (6.7 × 10⁶ GXCPC1, N = 5) and high dose (4 × 10⁷ GXCPC1, N = 6). The primary endpoint was safety, which was evaluated by recording adverse events throughout the trial; the secondary endpoints included total, pain, stiffness, and function subscales of the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Visual Analogue Scale (VAS) for pain, and 12-Item Short Form (SF-12) health survey questionnaire. The GXCPC1 treatment was found to be safe after 1 year of follow-up with no treatment-related severe adverse events observed. When compared to baseline, subjects in both the low- and high-dose cohorts demonstrated improving trends in pain and knee function after receiving GXCPC1 treatment. Generally, the net change in pain (95% confidence interval (CI) = -7.773 to -2.561t at 12 weeks compared to baseline) and knee function (95% CI = -24.297 to -10.036t at 12 weeks compared to baseline) was better in subjects receiving high-dose GXCPC1. Although this study included a limited number of subjects without a placebo arm, it showed that the intra-articular injection of ADSCs was safe and well-tolerated in subjects with therapeutic alternatives to treat knee OA. However, a larger scale study with an appropriate control would be necessary for clinical efficacy in the following study.

Trial registration: ClinicalTrials.gov NCT03943576.

Keywords: GXCPC1; allogeneic adipose-derived mesenchymal stem cells (ADSCs); knee osteoarthritis; safety; tolerability.

Figure 1.

Study schedule and schema of study subject disposition. (A) Study schedule. (B) Schema of study subject disposition. ADSC: adipose-derived mesenchymal stem cells; SF-12: 12-item Short Form; VAS: Visual Analogue Scale; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index.

Figure 2.

Net changes in WOMAC from baseline to 24 weeks after intra-articular injection of GXCPC1. (A) WOMAC total score, (B) WOMAC pain score, (C) WOMAC stiffness score, and (D) WOMAC physical function score. The data are presented by mean and error bars indicate standard deviation. WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index. *: Sign of significant difference in the high-dose cohort.

Figure 3.

Net changes in VAS for pain from baseline to 24 weeks after intra-articular injection of GXCPC1. The data are presented as mean and error bars indicate standard deviation. VAS: Visual Analogue Scale. *, #: Sign of significant difference in the high-dose cohort and low-dose cohort, respectively.

Figure 4.

Changes in SF-12 during 24 weeks after intra-articular injection of GXCPC1. (A) PCS. (B) MCS. The data are presented as mean and error bars indicate standard deviation. MCS: mental component summary; PCS: physical component summary. *: Sign of significant difference in the high-dose cohort.