Allogeinic Cellular Therapy for Degenerative Disc Disease: Hope or Hype?

Nov 21, 1998
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First, read this thread, then read this study:​


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​


Author links open overlay panelKasraAmirdelfanMDaHyunBaeMDbToryMcJunkinMDcMichaelDePalmaMDdKeeKimMDeWilliam J.BeckworthMDfGaryGhiselliMDgJames ScottBainbridgeMDg1RandallDryerMDhTimothy R.DeerMDiRoger D.BrownBAjaIPM Medical Group, Inc., 450 Wiget Lane, Walnut Creek, CA 94598, USAbThe Spine Institute, 2811 Wilshire Blvd, Suite 850, Santa Monica, CA 90403, USAcArizona Pain Specialists, 9787 N. 91st St, Suite 101, Scottsdale, AZ 85258, USAdVirginia Spine Research Institute, Inc., 9020 Stony Point Parkway, Suite 140, Richmond, VA 23235, USAeUC Davis Spine Center, 3301 C St, Suite 1500, Sacramento, CA 95816, USAfDepartment of Orthopaedics, Emory University School of Medicine, 59 Executive Park South, Suite 3000, Atlanta, GA 30329, USAgDenver Spine, 7800 E. Orchard Rd, Suite 100, Greenwood Village, CO 80111, USAhCentral Texas Spine Institute, 6818 Austin Center Blvd, Suite 200, Austin, TX 78731, USAiThe Center for Pain Relief, Inc., 400 Court St, Suite 100, Charleston, WV 25301, USAjMesoblast Inc., 12912 Hill Country Blvd, Building F, Suite 230, Bee Cave, TX 78738, USA
Received 10 December 2019, Revised 1 October 2020, Accepted 2 October 2020, Available online 9 October 2020.
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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.

Keywords​

Cell therapy
DDD
Low back pain
Mesenchymal precursor cells
Mesenchymal stem cells
Regenerative medicine
 
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What's fraudulent or being mis-represented?
Well, it’s not that it’s fraudulent but it’s how the data was being interpreted to inflate the products performance. I take no issue with the product but I am wondering where you stand on it?
 

Ducttape

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his position has consistently been one of support for regenerative medicine.


concerns with this study:
1. the stated conclusions are not the intended purpose of the study. this was a Phase 1b/2a study. specifically:
The study was designed to provide an initial assessment of safety, determine if MPC treatment has the potential for improving CLBP and function, and to generate hypotheses regarding the use of MPCs that could be further explored in future studies.
The sample size of 100 subjects was chosen to provide an assessment of the safety of injection of allogeneic MPCs injected into a degenerated intervertebral disk and to determine if there was an indication of radiographic, pain, and/or functional improvement. As appropriate for an early-phase study, the planned sample size was not prospectively powered but was conducted with enough subjects in each treatment group to determine if a larger future prospectively powered study should be conducted.
i see no disclaimer that this study was only an investigational study, only that there were positive conclusions.
2. it was blinded to the subject and the radiologic reviewer, but not the study investigator, proceduralist or staff.
3. there was a noticeable difference between the study groups.

There were statistically significant differences between treatment groups for the following baseline characteristics: sex, age, smoking status, body mass index, and duration of DDD ( Table 1 ). Fifty-three percent (n=53) of all subjects were male, though the 18 million MPC group had a greater proportion of males (70.0%) than the other three study arms. There was a greater proportion of never smokers in the 6 million and 18 million MPC groups (83.3% and 60.0%, respectively) compared with the saline and HA control groups (45.0% and 40.0%, respectively).
Subjects with any TEAE leading to discontinuation002 (6.7)2 (6.7)
Subjects with any TEAE related to study treatment1 (5.0)3 (15.0)6 (20.0)15 (50.0)
Subjects with any TEAE related to study procedure03 (15.0)6 (20.0)10 (33.3)
(first two columns are controls, 2nd to columns are MPC).

All study groups showed improvement from baseline at all time points in the prespecified and PTI-corrected analyses.

In the prespecified Mean VAS score analyses, 6 million MPC was superior to saline at 24 months (p=0.010) and HA at 3 and 6 months (p=0.008 and p=0.029); whereas the 18 million MPC group was superior to only HA at 12 months (p=0.048). In the PTI-corrected analyses, 6 million MPC showed significant Mean VAS score improvement compared with saline at 12, 24, and 36 months (p=0.018, p=0.005, and p=0.047) and was significant compared with HA at 3 and 6 months (p=0.005 and p=0.032). Similarly, 18 million MPC was superior to saline at 12, 24, and 36 months (p=0.024, p=0.028, and p=0.006) and was significant compared with HA at 3 months (p=0.033).

In the prespecified VAS Mean Change analyses, 6 million MPC was superior to saline at 24 months (p=0.012) and HA at 3 months (p=0.017) while 18 million MPC was superior to saline at 36 months (p=0.046). In comparison, the PTI-corrected analyses showed 6 million MPC superior to saline at 12 and 24 months (p=0.018 and p=0.006) and HA at 3 months (p=0.011), and 18 million MPC was superior to saline at 12, 24, and 36 months (p=0.011, p=0.014, and p=0.003) and superior to HA at 3 months (p=0.037).\



ultimately, with all those stats - MPC done by non-blinded investigators was superior to Saline at almost all standpoints, but only superior to HA at 3 months.


4. now, read the conclusions in the article - which holds to the purpose of the study and compare the statement with the conclusions in the summary.

Article:

Conclusions​

Results demonstrate that intradiscal injection of MPCs appears to be safe and may be an effective and durable minimally invasive therapy for subjects who have CLBP associated with moderate DDD. Further study in a larger blinded prospective randomized clinical trial that addresses the limitations of this initial clinical trial is warranted.

Summary - what everyone reads - implies that it is a Level 1 EBM and seems to me to gloss over that it is a preliminary study to assess for safety:

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
 
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Nov 21, 1998
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his position has consistently been one of support for regenerative medicine.


concerns with this study:
1. the stated conclusions are not the intended purpose of the study. this was a Phase 1b/2a study. specifically:


i see no disclaimer that this study was only an investigational study, only that there were positive conclusions.
2. it was blinded to the subject and the radiologic reviewer, but not the study investigator, proceduralist or staff.
3. there was a noticeable difference between the study groups.



(first two columns are controls, 2nd to columns are MPC).

All study groups showed improvement from baseline at all time points in the prespecified and PTI-corrected analyses.

In the prespecified Mean VAS score analyses, 6 million MPC was superior to saline at 24 months (p=0.010) and HA at 3 and 6 months (p=0.008 and p=0.029); whereas the 18 million MPC group was superior to only HA at 12 months (p=0.048). In the PTI-corrected analyses, 6 million MPC showed significant Mean VAS score improvement compared with saline at 12, 24, and 36 months (p=0.018, p=0.005, and p=0.047) and was significant compared with HA at 3 and 6 months (p=0.005 and p=0.032). Similarly, 18 million MPC was superior to saline at 12, 24, and 36 months (p=0.024, p=0.028, and p=0.006) and was significant compared with HA at 3 months (p=0.033).

In the prespecified VAS Mean Change analyses, 6 million MPC was superior to saline at 24 months (p=0.012) and HA at 3 months (p=0.017) while 18 million MPC was superior to saline at 36 months (p=0.046). In comparison, the PTI-corrected analyses showed 6 million MPC superior to saline at 12 and 24 months (p=0.018 and p=0.006) and HA at 3 months (p=0.011), and 18 million MPC was superior to saline at 12, 24, and 36 months (p=0.011, p=0.014, and p=0.003) and superior to HA at 3 months (p=0.037).\



ultimately, with all those stats - MPC done by non-blinded investigators was superior to Saline at almost all standpoints, but only superior to HA at 3 months.


4. now, read the conclusions in the article - which holds to the purpose of the study and compare the statement with the conclusions in the summary.

Article:


Summary - what everyone reads - implies that it is a Level 1 EBM and seems to me to gloss over that it is a preliminary study to assess for safety:

Thank you for acknowledging my consistency. I feel seen.
 
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I wasn’t suggesting that you didn’t support regenerative medicine but more so asking if your analysis had at all changed based on the most recent trial. I am eagerly anticipating the results of their European phase 3 trial. Take care
 
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