TY - JOUR
T1 - Allogeneic mesenchymal precursor cells treatment for chronic low back pain associated with degenerative disc disease
T2 - a prospective randomized, placebo-controlled 36-month study of safety and efficacy
AU - Amirdelfan, Kasra
AU - Bae, Hyun
AU - McJunkin, Tory
AU - DePalma, Michael
AU - Kim, Kee
AU - Beckworth, William J.
AU - Ghiselli, Gary
AU - Bainbridge, James Scott
AU - Dryer, Randall
AU - Deer, Timothy R.
AU - Brown, Roger D.
N1 - Funding Information:
Funding: KA, HB, TM, MD, KK, WJB, GG, JSB, TD: Institutional grant from Mesoblast Ltd. to support trial participation and execution; RDB: Receives salary and stock-based compensation as employee of Mesoblast Ltd.
Funding Information:
In addition, this study was funded by Mesoblast; nine authors received institutional grants from Mesoblast to support trial-related expenses and oneone author receives cash and stock-based compensation as an employee of Mesoblast; one author did not have any financial association with the current work. Although the study was funded by Mesoblast, all authors reviewed the analysis, interpretation, and conclusions to ensure integrity. Additionally, the study was conducted under an Investigational New Drug application and US FDA oversight. All study subjects and radiographic reviewers were blinded to treatment assignment throughout the full 36-month follow-up period.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Cell therapy
KW - DDD
KW - Low back pain
KW - Mesenchymal precursor cells
KW - Mesenchymal stem cells
KW - Regenerative medicine
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U2 - 10.1016/j.spinee.2020.10.004
DO - 10.1016/j.spinee.2020.10.004
M3 - Article
C2 - 33045417
AN - SCOPUS:85093699863
JO - Spine Journal
JF - Spine Journal
SN - 1529-9430
ER -