From the Department of Neurological Surgery (D.O.O.), University of Pittsburgh Medical Center, PA; New England Institute for Neurology and Headache (P.M.), Stamford, CT; Department of Neurosurgery (A.S.A.), Loma Linda University Medical Center, CA; Department of Neurosurgery (Y.K.), The University of Tokyo Hospital, Japan; Department of Neurosurgery (M.K.), Hokkaido University Hospital, Sapporo, Japan; Department of Neurology (S.C.C.), University of California, Los Angeles; Westview Clinical Research (A.L.), Placentia, CA; Department of Translational Neurosciences (S.K.), Providence Saint John's Health Center, Santa Monica, CA; The Neurology Center of Southern California (B.M.F.), Carlsbad, CA; Department of Neurology (L.I.G.), University of California, Irvine; UCSF Weill Institute for Neurosciences (A.S.K.), Department of Neurology, University of California, San Francisco; Department of Neurology and Neurological Sciences (N.E.S.), and Stanford Stroke Center, Stanford University School of Medicine and Stanford Health Care, CA; Department of Neurological Surgery (J.W.C.), University of California, Irvine; JCHO Tokyo Shinjuku Medical Center (H.I.), Japan; Department of Neurological Surgery (T.Y.), Okayama University Graduate School of Medicine, Japan; SanBio, Inc. (D.C., B.N., D.B.), Mountain View, CA; Watson & Stonehouse Enterprises LLC (A.H.S.), Pacific Grove, CA; Massachusetts General Hospital and Harvard Medical School (R.M.R.), Boston; Department of Neurosurgery and Stanford Stroke Center (G.K.S.), Stanford University School of Medicine and Stanford Health Care, CA; Biostatistical Consulting Inc. (E.C.P.), Mountain View, CA; and Neurotrauma Rehabilitation Associates LLC (A.H.W.), Littleton, CO.
Neurology. 2024 Oct 8;103(7):e209797. doi: 10.1212/WNL.0000000000209797. Epub 2024 Sep 4.
Traumatic brain injury (TBI) is frequently characterized by chronic motor deficits. Therefore, this clinical trial assessed whether intracranial implantation of allogeneic modified mesenchymal stromal (SB623) cells can improve chronic motor deficits after TBI.
Post hoc analysis of the double-blind, randomized, prospective, surgical sham-controlled, phase 2, STEMTRA clinical trial (June 2016 and March 2019) with 48 weeks of follow-up was conducted. In this international, multicenter clinical trial, eligible participants had moderate-to-severe TBI, were ≥12 months postinjury, and had chronic motor deficits. Participants were randomized in a 1:1:1:1 ratio to stereotactic surgical intracranial implantation of SB623 cells (2.5 × 10, 5.0 × 10, 10 × 10) or surgical sham-controlled procedure. The prespecified primary efficacy end point was significantly greater change from baseline of the Fugl-Meyer Motor Scale (FMMS) score, a measure of motor status, for the SB623 pooled vs control arm at 24 weeks.
A total of 211 participants were screened, 148 were excluded, and 63 underwent randomization, of which 61 (97%; mean age, 34 [SD, 12] years; 43 men [70.5%]) completed the trial. Single participants in the SB623 2.5 × 10 and 5.0 × 10 cell dose groups discontinued before surgery. Safety and efficacy (modified intent-to-treat) were assessed in participants who underwent surgery (N = 61; SB623 = 46, controls = 15). The primary efficacy end point (FMMS) was achieved (least squares mean [SE] SB623: +8.3 [1.4]; 95% CI 5.5-11.2 vs control: +2.3 [2.5]; 95% CI -2.7 to 7.3; = 0.04), with faster improvement of the FMMS score in SB623-treated groups than in controls at 24 weeks and sustained improvement at 48 weeks. At 48 weeks, improvement of function and activities of daily living (ADL) was greater, but not significantly different in SB623-treated groups vs controls. The incidence of adverse events was equivalent in SB623-treated groups and controls. There were no deaths or withdrawals due to adverse events.
Intraparenchymal implantation of SB623 cells was safe and significantly improved motor status at 24 weeks in participants with chronic motor deficits after TBI, with continued improvement of function and ADL at 48 weeks. Cell therapy can modify chronic neurologic deficits after TBI.
ClinicalTrials.gov Identifier: NCT02416492. Submitted to registry: April 15, 2015. First participant enrolled: July 6, 2016. Available at: classic.clinicaltrials.gov/ct2/show/NCT02416492.
This study provides Class I evidence that intracranial implantation of allogeneic stem (SB623) cells in adults with motor deficits from chronic TBI improves motor function at 24 weeks.
创伤性脑损伤（TBI）常伴有慢性运动功能障碍。因此，本临床试验评估了颅内植入同种异体修饰间充质基质（SB623）细胞是否能改善 TBI 后的慢性运动功能障碍。
对双盲、随机、前瞻性、手术假对照、2 期 STEMTRA 临床试验（2016 年 6 月至 2019 年 3 月）的事后分析，随访 48 周。在这项国际性、多中心临床试验中，合格的参与者有中度至重度 TBI，受伤后≥12 个月，且有慢性运动功能障碍。参与者以 1:1:1:1 的比例随机分为立体定向手术颅内植入 SB623 细胞（2.5×10、5.0×10、10×10）或手术假对照程序。预设的主要疗效终点是 SB623 组与对照组相比，24 周时 Fugl-Meyer 运动量表（FMMS）评分的变化有显著差异，FMMS 是运动状态的一种测量方法。
共筛选了 211 名参与者，其中 148 名被排除，63 名参与者接受了随机分组，其中 61 名（97%；平均年龄 34 [标准差 12] 岁；43 名男性[70.5%]）完成了试验。SB623 2.5×10 和 5.0×10 细胞剂量组各有 1 名参与者在手术前退出。接受手术的参与者（N=61；SB623=46，对照组=15）进行了安全性和疗效（改良意向治疗）评估。主要疗效终点（FMMS）达到（最小二乘均数[SE] SB623：+8.3[1.4]；95%CI 5.5-11.2 比对照组：+2.3[2.5]；95%CI-2.7 至 7.3； = 0.04），SB623 治疗组在 24 周时 FMMS 评分改善更快，在 48 周时持续改善。48 周时，SB623 治疗组的功能和日常生活活动（ADL）改善更大，但与对照组无显著差异。SB623 治疗组与对照组的不良事件发生率相当。没有因不良事件而死亡或退出。
SB623 细胞脑内植入在 TBI 后慢性运动功能障碍的参与者中是安全的，可显著改善 24 周时的运动状态，并在 48 周时持续改善功能和 ADL。细胞疗法可改变 TBI 后的慢性神经功能障碍。
ClinicalTrials.gov 标识符：NCT02416492。向注册处提交日期：2015 年 4 月 15 日。首次入组参与者日期：2016 年 7 月 6 日。可在：classic.clinicaltrials.gov/ct2/show/NCT02416492。
这项研究提供了 1 级证据，表明颅内植入同种异体干细胞（SB623）可改善慢性 TBI 成人的运动功能，在 24 周时改善运动功能。
