Kasra Amirdelfan1, Hyun Bae2, Tory McJunkin3, Michael DePalma4, Kee Kim5, William J Beckworth6, Gary Ghiselli7, James Scott Bainbridge7, Randall Dryer8, Timothy R Deer9, Roger D Brown10. 1. IPM Medical Group, Inc., 450 Wiget Lane, Walnut Creek, CA 94598, USA. Electronic address: kasdaq@gmail.com. 2. The Spine Institute, 2811 Wilshire Blvd, Suite 850, Santa Monica, CA 90403, USA. 3. Arizona Pain Specialists, 9787 N. 91st St, Suite 101, Scottsdale, AZ 85258, USA. 4. Virginia Spine Research Institute, Inc., 9020 Stony Point Parkway, Suite 140, Richmond, VA 23235, USA. 5. UC Davis Spine Center, 3301 C St, Suite 1500, Sacramento, CA 95816, USA. 6. Department of Orthopaedics, Emory University School of Medicine, 59 Executive Park South, Suite 3000, Atlanta, GA 30329, USA. 7. Denver Spine, 7800 E. Orchard Rd, Suite 100, Greenwood Village, CO 80111, USA. 8. Central Texas Spine Institute, 6818 Austin Center Blvd, Suite 200, Austin, TX 78731, USA. 9. The Center for Pain Relief, Inc., 400 Court St, Suite 100, Charleston, WV 25301, USA. 10. Mesoblast Inc., 12912 Hill Country Blvd, Building F, Suite 230, Bee Cave, TX 78738, USA.
Abstract
BACKGROUND CONTEXT PURPOSE: Evaluate the safety and efficacy of a single intradiscal 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-month follow-up. STUDY DESIGN/ SETTING: A multicenter, randomized, controlled study conducted at 13 clinical sites (12 in the United States and 1 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 3 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 postinjection. 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 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 application sponsored and funded by Mesoblast. 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 time points through 36 months. Additionally, the proportion of subjects achieving the minimally important change and clinically significant change 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, 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 intradiscal injection of MPCs could be a safe, effective, durable, and minimally invasive therapy for subjects who have CLBP associated with moderate DDD.
RCT Entities:
BACKGROUND CONTEXT PURPOSE: Evaluate the safety and efficacy of a single intradiscal 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-month follow-up. STUDY DESIGN/ SETTING: A multicenter, randomized, controlled study conducted at 13 clinical sites (12 in the United States and 1 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 3 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 postinjection. 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 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 application sponsored and funded by Mesoblast. 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 time points through 36 months. Additionally, the proportion of subjects achieving the minimally important change and clinically significant change 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, 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 intradiscal injection of MPCs could be a safe, effective, durable, and minimally invasive therapy for subjects who have CLBP associated with moderate DDD.
Authors: Alisa L Dutmer; Remko Soer; André P Wolff; Michiel F Reneman; Maarten H Coppes; Henrica R Schiphorst Preuper Journal: Eur Spine J Date: 2022-01-19 Impact factor: 3.134