40. Disc progenitor cell therapy improves pain, disability, and quality of life for patients with lumbar disc degeneration: results of an FDA-approved clinical trial

Abstract

BACKGROUND CONTEXT Allogeneic disc progenitor cells derived from adult intervertebral disc tissue have demonstrated both immunomodulatory and regenerative properties in preclinical animal studies. This includes the ability to increase aggrecan and collagen production and restore disc histology. These cells have the potential to impact the pathophysiology of degenerative disc disease (DDD) and lead to lasting pain relief and improved quality of life for patients with symptomatic DDD. PURPOSE To report the results of an FDA-approved clinical trial of injectable allogeneic disc progenitor cells and a viscous carrier for the treatment of DDD vs carrier and saline controls. STUDY DESIGN/SETTING A randomized, double-blind, placebo-controlled study at 13 clinical sites. PATIENT SAMPLE Sixty subjects (mean age 38, 60% male) were enrolled. OUTCOME MEASURES Subjects were assessed using validated safety and efficacy parameters including low-back pain visual analog scale (VAS), Oswestry Disability Index (ODI) and EQ-5D. METHODS Subjects with early to moderate, symptomatic lumbar DDD were randomized to one of four treatment groups and received single intradiscal injections of either low-dose cells (3,000,000cells/mL; N=20), high-dose cells (9,000,000cells/mL; N=20), vehicle alone (N=10) or placebo (N=10). Subject outcomes were assessed over 52 weeks. RESULTS VAS scores in the high-dose cell group were statistically significantly improved over baseline at weeks 12 (-54.53% [-69.46, -39.60], p=0.0056), 26 (-50.94% [-66.10, -35.78], p=0.0140), and 52 (-62.79% [90% CI -77.13, -48.46], p=0.0005). The vehicle group achieved statistical significance in VAS at week 52 only (-52.83% [90%CI -74.73, -30.92], p=0.0443). Mean pain VAS improved from baseline after treatment but only achieved statistical significance at week 26 with low-dose cells (-48.49% [90% CI -61.03, -35.94], p=0.0101) and saline (-50.13% [-65.24, -35.02], p=0.0206); neither demonstrated statistical significance at week 52. Further analysis showed that only the high-dose cell group showed reduction from baseline in back pain VAS that was statistically significantly greater than a minimum clinically important difference (MCID) of -20mm at week 52 (-39.8 [-50.0, -29.6], p=0.0001). Only the high-dose cell group exhibited an improvement from baseline in ODI score at week 52 that was statistically significantly greater than a MCID of -10 points (-24.3[-31.2, -17.5], p <0.0001) and an EQ-5D index score that was statistically significantly greater than a MCID of 0.08 (0.194 [0.139, 0.250], p <0.0001). CONCLUSIONS High-dose allogeneic disc progenitor cells produced meaningful, statistically significant improvements in back pain VAS, ODI and EQ-5D at one-year post-intradiscal injection. FDA DEVICE/DRUG STATUS IDCT - Injectable Discogenic Cell Therapy (Investigational/Not Approved) Allogeneic disc progenitor cells derived from adult intervertebral disc tissue have demonstrated both immunomodulatory and regenerative properties in preclinical animal studies. This includes the ability to increase aggrecan and collagen production and restore disc histology. These cells have the potential to impact the pathophysiology of degenerative disc disease (DDD) and lead to lasting pain relief and improved quality of life for patients with symptomatic DDD. To report the results of an FDA-approved clinical trial of injectable allogeneic disc progenitor cells and a viscous carrier for the treatment of DDD vs carrier and saline controls. A randomized, double-blind, placebo-controlled study at 13 clinical sites. Sixty subjects (mean age 38, 60% male) were enrolled. Subjects were assessed using validated safety and efficacy parameters including low-back pain visual analog scale (VAS), Oswestry Disability Index (ODI) and EQ-5D. Subjects with early to moderate, symptomatic lumbar DDD were randomized to one of four treatment groups and received single intradiscal injections of either low-dose cells (3,000,000cells/mL; N=20), high-dose cells (9,000,000cells/mL; N=20), vehicle alone (N=10) or placebo (N=10). Subject outcomes were assessed over 52 weeks. VAS scores in the high-dose cell group were statistically significantly improved over baseline at weeks 12 (-54.53% [-69.46, -39.60], p=0.0056), 26 (-50.94% [-66.10, -35.78], p=0.0140), and 52 (-62.79% [90% CI -77.13, -48.46], p=0.0005). The vehicle group achieved statistical significance in VAS at week 52 only (-52.83% [90%CI -74.73, -30.92], p=0.0443). Mean pain VAS improved from baseline after treatment but only achieved statistical significance at week 26 with low-dose cells (-48.49% [90% CI -61.03, -35.94], p=0.0101) and saline (-50.13% [-65.24, -35.02], p=0.0206); neither demonstrated statistical significance at week 52. Further analysis showed that only the high-dose cell group showed reduction from baseline in back pain VAS that was statistically significantly greater than a minimum clinically important difference (MCID) of -20mm at week 52 (-39.8 [-50.0, -29.6], p=0.0001). Only the high-dose cell group exhibited an improvement from baseline in ODI score at week 52 that was statistically significantly greater than a MCID of -10 points (-24.3[-31.2, -17.5], p <0.0001) and an EQ-5D index score that was statistically significantly greater than a MCID of 0.08 (0.194 [0.139, 0.250], p <0.0001). High-dose allogeneic disc progenitor cells produced meaningful, statistically significant improvements in back pain VAS, ODI and EQ-5D at one-year post-intradiscal injection.