214. Viable allograft supplement for disc degeneration: measurable disc height increases at 12 months in first 24 subjects

Abstract

BACKGROUND CONTEXT Degenerative disc disease and discogenic back pain are ubiquitously common and the leading cause of disability in the United States; affecting over a quarter of a billion people worldwide, threatening quality of life, and increasing the risk of significant morbidity. Conventional or current treatments including expanded stem cell delivery to the intervertebral disc have been shown to be effective in small series and clinical trials but there remains a paucity of clinical evidence showing the benefits of disc structural cellular allograft supplementation in larger randomized controlled trials. PURPOSE To demonstrate clinical evidence showing the benefits of disc structural cellular allograft supplementation. STUDY DESIGN/SETTING A total of 236 subjects with painful discogenic low back pain were screened at 13 U.S. sites with 218 divided into a treatment group, a nonsurgical management (NSM) group, and a placebo control group with a 3.5:1:1 randomization ratio. PATIENT SAMPLE This study compares 199 enrolled patients. Subjects consisted of 86 females and 113 males; demographics of age 42.9 (27-62), and BMI 27 (17.7-35.4) OUTCOME MEASURES Two co-primary endpoints; back pain visual analog scale (VAS) and Oswestry Disability Index (ODI) were evaluated along with safety data including reported adverse events (AEs) and changes in clinical laboratory evaluations. Data was collected at baseline, and at 3, 6 and 12 months. Structural outcomes were evaluated by x-rays and Magnetic Resonance Imaging (MRI) at 6 and at 12 months for Pfirrmann Rating and for disc height change. METHODS A total of 236 subjects with painful discogenic low back pain were screened at 13 U.S. sites with 218 divided into a treatment group, a nonsurgical management (NSM) group, and a placebo control group with a 3.5:1:1 randomization ratio. Subjects in the study were treated at either one or two levels. The first 24 participants were assessed 1 month visit after enrollment. Two co-primary endpoints; back pain VAS and ODI were evaluated along with safety data including reported AEs and changes in clinical laboratory evaluations. Data was collected at baseline, and at 3, 6 and 12 months. Structural outcomes were evaluated by x-rays and magnetic resonance imaging (MRI) at 6 and at 12 months for Pfirrmann Rating and for disc height change. This trial is registered on www.clinicaltrials.gov (NCT03709901). RESULTS At the 6- and 12-month time points in the safety cohort, VAS back pain improved from 54.81, 55.25 and 62.25 in the allograft, placebo and NSM subjects respectively to 16.0, 41.0, and 6.67 at 6 months, and 12.27, 19.67 and 6.0 at 12 months. At the 6- and 12-month time points, ODI improved from 53.73, 49.25 and 55.75 in the allograft, placebo and NSM subjects respectively to 18.47, 28.75, and 19.0 at 6 months and 15.67, 9.33 and 11.0 at 12 months. The largest gains were made in the open-label cross over subjects. MRI imaging demonstrated that pain remission and functional improvement were not correlated with Pfirrmann Grade. Measurement of disc height demonstrated a net increase for all subjects randomized to the active allograft; total disc heights of the allograft treated increased from 40.15 to 41.58 compared to those treated by placebo 40.01 to 41.08. Open label cross-over showed the greatest improvement from the 1-month visit of 42.05 to 46.02. Retention or increase in disc height was related to the number of levels treated; those subjects treated at 2 levels increased disc height not only at the levels treated but at all intervertebral disc levels rostral to the intervention. CONCLUSIONS Subjects in this large triple-arm prospective randomized control trial showed that percutaneous delivery of an allogeneic disc tissue matrix can be done safely with limited AEs. The prominent improvements in pain and function were coupled with similar increases in intervertebral disc height that was correlated with the number of disc levels treated but not related to Pfirrmann grade interpretation. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.