Efficacy and Safety of Allogeneic Mesenchymal Precursor Cells with and Without Hyaluronic Acid for Treatment of Chronic Low Back Pain: A Prospective, Randomized, Double Blind, Concurrent-Controlled 36-Month Study

Purpose: Evaluate the efficacy and safety of a single injection of mesenchymal precursor cells (MPCs) with or without hyaluronic acid (HA) compared to an intradiscal saline injection through 36 months follow-up in subjects with chronic low back pain (CLBP) associated with moderate DDD (mDDD).

Materials and Methods: A prospective, multicenter, randomized, double-blind, controlled study conducted at 49 clinical sites. A total of 404 subjects with CLBP associated with mDDD at one level from L1 to S1 received MPCs without HA (MPC), MPCs with HA (MPC+HA), or saline control (control) treatment. Subjects were clinically (VAS, ODI and EQ-5D-5L index) evaluated at 1,3,6,12,18,24&36 months post-injection. The primary efficacy endpoint was a composite responder analysis for overall treatment success at both 12 and 24 months that was comprised of: (1) at least a 50% reduction from baseline in low back pain VAS score (average pain over 24 hours); (2) at least a 15-point decrease from baseline in ODI score; and (3) no adjudicated post-treatment interventions at the treated level.

Results: All treatment groups showed substantial improvement from baseline in LS Mean LBP and ODI. Although the trial did not meet the primary composite endpoint, MPC+HA significantly reduced lower back pain at 12 and 24 months compared to control. The results observed in all subjects were enhanced for MPC+HA and MPC in the pre-specified CLBPLTM subgroup with MPC+HA having significantly greater reduction in LBP at all time points compared to control and MPC having significantly greater reduction in LBP at 6, 12 and 36 months. In the CLBPLTM subgroup, MPC+HA led to significantly greater pain response, functional improvement, and quality of life enhancements compared to control at multiple time points. MPC+HA baseline opioid users also exhibited greater reductions in opioid use and more patients opioid-free at 36 months compared to the control group. The injection and MPC treatment were well tolerated, with no treatment-related serious adverse events and similar rates of post-treatment interventions across groups.

Conclusion: MPC+HA treatment showed a significant reduction in pain compared to control that was enhanced in subjects with CLBP duration less than 68 months. Intra-discal injection of MPC+HA is a minimally invasive non-opioid therapy that appears to be safe and demonstrates reduction in pain through 24 months compared to control with enhanced results in subjects with mDDD that have had CLBP less than 68 months.