Gornet Matthew F, Beall Douglas P, Davis Timothy T, Coric Domagoj, LaBagnara Michael, Krull Angela, DePalma Michael J, Hsieh Patrick C, Mallempati Srinivas, Schranck Francine W, Kelly Colleen, Foley Kevin T
The Orthopedic Center of St. Louis, St. Louis, MO, USA.
Clinical Radiology of Oklahoma, Edmond, OK, USA.
Int J Spine Surg. 2024 Jul 4;18(3):237-248. doi: 10.14444/8609.
Progenitor cells derived from intervertebral disc tissue demonstrated immunomodulatory and regenerative properties in preclinical studies. We report the safety and efficacy results of a US Food and Drug Administration-approved clinical trial of these cells for the treatment of symptomatic degenerative disc disease.
Sixty patients with symptomatic single-level lumbar degenerative disc disease (mean age 37.9 years, 60% men) were enrolled in a randomized, double-blinded, placebo-controlled Phase I/Phase II study at 13 clinical sites. They were randomized to receive single intradiscal injections of either low-dose cells ( = 20), high-dose cells ( = 20), vehicle alone ( = 10), or placebo ( = 10). The primary endpoint was mean visual analog scale (VAS) pain improvement >30% at 52 weeks. Disc volume was radiologically assessed. Adverse events (AEs), regardless of whether they were related to treatment, were reported. Patients were assessed at baseline and at 4, 12, 26, 52, 78, and 104 weeks posttreatment.
At week 52, the high-dose group had a mean VAS percentage decrease from baseline (-62.8%, = 0.0005), achieving the endpoint of back pain improvement >30%; the mean change was also significantly greater than the minimal clinically important difference of a 20-point decrease (-42.8, = 0.001). This clinical improvement was maintained at week 104. The vehicle group had a smaller significant decrease in VAS (-52.8%, = 0.044), while the low-dose and placebo groups showed nonsignificant improvements. Only the high-dose group had a significant change in disc volume, with mean increases of 249.0 mm ( = 0.028) at 52 weeks and 402.1 mm ( = 0.028) at 104 weeks. A minority of patients (18.3%) reported AEs that were severe. Overall, 6.7% of patients experienced serious AEs, all in the vehicle ( = 1) or placebo ( = 3) groups, none treatment related.
High-dose allogeneic disc progenitor cells produced statistically significant, clinically meaningful improvements in back pain and disc volume at 1 year following a single intradiscal injection and were safe and well tolerated. These improvements were maintained at 2 years post-injection.
NCT03347708-Study to Evaluate the Safety and Preliminary Efficacy of Injectable Disc Cell Therapy, a Treatment for Symptomatic Lumbar Intervertebral Disc Degeneration.
在临床前研究中，源自椎间盘组织的祖细胞表现出免疫调节和再生特性。我们报告了美国食品药品监督管理局批准的一项关于这些细胞治疗症状性退行性椎间盘疾病的临床试验的安全性和有效性结果。
60例有症状的单节段腰椎退行性椎间盘疾病患者（平均年龄37.9岁，60%为男性）在13个临床地点参加了一项随机、双盲、安慰剂对照的I/II期研究。他们被随机分组，接受单次椎间盘内注射低剂量细胞（n = 20）、高剂量细胞（n = 20）、单独载体（n = 10）或安慰剂（n = 10）。主要终点是在52周时视觉模拟量表（VAS）疼痛改善均值>30%。通过影像学评估椎间盘体积。报告不良事件（AE），无论其是否与治疗相关。在基线以及治疗后4、12、26、52、78和104周对患者进行评估。
在第52周时，高剂量组VAS均值较基线下降百分比为（-62.8%，P = 0.0005），达到背痛改善>30%的终点；平均变化也显著大于最小临床重要差异即下降20分（-42.8，P = 0.001）。这种临床改善在第104周时得以维持。载体组VAS有较小的显著下降（-52.8%，P = 0.044），而低剂量组和安慰剂组显示改善不显著。只有高剂量组椎间盘体积有显著变化，在52周时平均增加249.0 mm³（P = 0.028），在104周时增加402.1 mm³（P = 0.028）。少数患者（18.3%）报告了严重的不良事件。总体而言，6.7%的患者经历了严重不良事件，均在载体组（n = 1）或安慰剂组（n = 3），均与治疗无关。
单次椎间盘内注射后1年，高剂量同种异体椎间盘祖细胞在背痛和椎间盘体积方面产生了具有统计学意义且临床有意义的改善，并且安全且耐受性良好。这些改善在注射后2年得以维持。
NCT03347708 - 评估可注射椎间盘细胞疗法治疗症状性腰椎间盘退变的安全性和初步有效性的研究。
