Allogeneic Mesenchymal Precursor Cells Treatment for Chronic Low Back Pain Associated with Degenerative Disc Disease: A Prospective Randomized, Placebo-Controlled 36-Month Study of Safety and Efficacy.

Abstract BACKGROUND CONTEXT PURPOSE Evaluate the safety and efficacy of a single injection of STRO-3+ adult allogeneic mesenchymal precursor cells (MPCs) combined with hyaluronic acid (HA) in subjects with chronic low back pain (CLBP) associated with degenerative disc disease (DDD) through 36 months follow-up. STUDY DESIGN/SETTING A multicenter, randomized, controlled study conducted at 13 clinical sites (12 in the United States and one in Australia). SUBJECT SAMPLE A total of 100 subjects with chronic low back pain associated with moderate DDD (modified Pfirrmann score of 3-6) at one level from L1 to S1 for at least 6 months and failing three months of conservative treatment, including physical therapy were randomized in a 3:3:2:2 ratio to receive 6 million MPCs with HA, 18 million MPCs with HA, HA vehicle control, or saline control (placebo) treatment. OUTCOME MEASURES Subjects were clinically and radiographically evaluated at 1, 3, 6, 12, 24, and 36 months post-injection. Subject reported outcomes including adverse events, LBP on a Visual Analog Scale (VAS), Oswestry Disability Index (ODI), SF-36 and Work Productivity and Activity Index (WPAI) were collected. METHODS Clinical and radiographic measures were collected at each visit. All randomized subjects were included in the safety assessments and analyzed based on the treatment received. Safety assessments included assessments of AEs, physical and radiographic examinations and laboratory testing. Efficacy assessments evaluated changes in VAS, ODI and modified Pfirrmann (MP) scores between all active and control groups respectively. Assessments included least squares mean (Mean), LS mean change from baseline (Mean Change) and responder analyses in order to assess the clinical significance of observed changes from baseline. The population for efficacy assessments was adjusted for the confounding effects of post-treatment interventions (PTIs). This study was conducted under an FDA Investigational New Drug (IND) application sponsored and funded by [identifying information removed for blinding purposes]. RESULTS There were significant differences between the control and MPC groups for improvement in VAS and ODI. The PTI corrected VAS and ODI Means and Mean Change analyses; the proportion of subjects with VAS ≥30% and ≥50% improvement from baseline; absolute VAS score ≤ 20; and ODI reduction ≥10 and ≥15 points from baseline showed MPC therapy superior to controls at various timepoints through 36 months. Additionally, the proportion of subjects achieving the minimally important change (MIC) and clinically significant change (CSC) composite endpoints for the MPC groups was also superior compared with controls at various time points from baseline to 36 months. There were no significant differences in change in MP score from baseline across the groups. There were also no statistically significant differences in change in modified MP score at the level above or below the level treated between study arms. Both the procedure and treatment were well tolerated and there were no clinical symptoms of immune reaction to allogeneic MPCs. There was a low rate of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and the rates of these events in the MPC groups were not significantly different from the control groups. One TEAE of severe back pain was possibly related to study agent and one TEAE of implantation site infection was considered to be related to the study procedure. CONCLUSIONS Results provide evidence that intra-discal injection of MPCs could be a safe, effective, durable and minimally invasive therapy for subjects who have CLBP associated with moderate DDD.