Abstract：
The primary objective of this study was to evaluate the safety of 3 escalating doses of oligodendrocyte progenitor cells (LCTOPC1; previously known as GRNOPC1 and AST-OPC1) administered at a single time point between 21 and 42 days postinjury to participants with subacute cervical spinal cord injuries (SCIs). The secondary objective was to evaluate changes in neurological function following administration of LCTOPC1.
This study was designed as an open-label, dose-escalation, multicenter clinical trial. Twenty-five participants with C4-7 American Spinal Injury Association Impairment Scale grade A or B injuries received a single dose of either 2 × 106, 1 × 107, or 2 × 107 LCTOPC1 delivered via intraparenchymal injection into the spinal cord at the site of injury using a custom-designed syringe positioning device. Low-dose tacrolimus was administered until day 60. Outcome measures included adverse event (AE) monitoring and neurological function as measured by the International Standards for Neurological Classification of Spinal Cord Injury.
All 25 participants experienced at least one AE, with a total of 534 AEs (32 study-related vs 502 study-unrelated anticipated complications of SCI) reported at the completion of 1-year follow-up. There were 29 serious AEs reported. Two grade 3 serious AEs (CSF leak in one participant and a bacterial infection in another) were considered related to the injection procedure and to immunosuppression with tacrolimus, respectively. The CSF leakage resolved with sequelae, including self-limited altered mental status, and the infection resolved with antibiotic therapy. For all participants, MRI scans demonstrated no evidence of an enlarging mass, spinal cord damage related to the injection procedure, inflammatory lesions in the spinal cord, or masses in the ventricular system. At 1-year follow-up, 21/22 (96%) of the intention-to-treat group recovered one or more levels of neurological function on at least one side of their body, and 7/22 (32%) recovered two or more levels of neurological function on at least one side of their body.
LCTOPC1 can be safely administered to participants in the subacute period after cervical SCI. The injection procedure, low-dose temporary immunosuppression regimen, and LCTOPC1 were well tolerated. The safety and neurological function data support further investigation to determine the efficacy of LCTOPC1 in the treatment of SCI. Clinical trial registration no.: NCT02302157 (ClinicalTrials.gov).
This study was designed as an open-label, dose-escalation, multicenter clinical trial. Twenty-five participants with C4-7 American Spinal Injury Association Impairment Scale grade A or B injuries received a single dose of either 2 × 106, 1 × 107, or 2 × 107 LCTOPC1 delivered via intraparenchymal injection into the spinal cord at the site of injury using a custom-designed syringe positioning device. Low-dose tacrolimus was administered until day 60. Outcome measures included adverse event (AE) monitoring and neurological function as measured by the International Standards for Neurological Classification of Spinal Cord Injury.
All 25 participants experienced at least one AE, with a total of 534 AEs (32 study-related vs 502 study-unrelated anticipated complications of SCI) reported at the completion of 1-year follow-up. There were 29 serious AEs reported. Two grade 3 serious AEs (CSF leak in one participant and a bacterial infection in another) were considered related to the injection procedure and to immunosuppression with tacrolimus, respectively. The CSF leakage resolved with sequelae, including self-limited altered mental status, and the infection resolved with antibiotic therapy. For all participants, MRI scans demonstrated no evidence of an enlarging mass, spinal cord damage related to the injection procedure, inflammatory lesions in the spinal cord, or masses in the ventricular system. At 1-year follow-up, 21/22 (96%) of the intention-to-treat group recovered one or more levels of neurological function on at least one side of their body, and 7/22 (32%) recovered two or more levels of neurological function on at least one side of their body.
LCTOPC1 can be safely administered to participants in the subacute period after cervical SCI. The injection procedure, low-dose temporary immunosuppression regimen, and LCTOPC1 were well tolerated. The safety and neurological function data support further investigation to determine the efficacy of LCTOPC1 in the treatment of SCI. Clinical trial registration no.: NCT02302157 (ClinicalTrials.gov).
摘要：
这项研究的主要目的是评估在亚急性颈脊髓损伤（SCI）参与者受伤后21至42天的单个时间点施用3种递增剂量的少突胶质细胞祖细胞（LCTOPC1；以前称为GRNOPC1和AST-OPC1）的安全性。次要目标是评估LCTOPC1给药后神经功能的变化。
这项研究被设计为开放标签，剂量递增，多中心临床试验。25名C4-7美国脊髓损伤协会损伤量表A级或B级损伤的参与者接受了单剂量的2×106、1×107或2×107LCTOPC1，通过实质内注射到脊髓中使用定制设计的注射器定位装置。给予低剂量他克莫司直至第60天。结果测量包括不良事件(AE)监测和神经功能,如通过脊髓损伤的神经分类的国际标准测量的。
所有25名参与者至少经历了一次AE，在1年随访结束时,共报告了534例AE(32例研究相关与502例研究无关的SCI预期并发症).报告29例严重不良事件。两个3级严重不良事件（一个参与者的CSF泄漏和另一个参与者的细菌感染）被认为与注射程序和他克莫司的免疫抑制有关。分别。脑脊液渗漏有后遗症，包括自我限制的精神状态改变，感染通过抗生素治疗解决。对于所有参与者，核磁共振扫描没有显示肿块扩大的证据,与注射过程有关的脊髓损伤，脊髓的炎性病变，或心室系统中的肿块。在1年的随访中，意向治疗组的21/22（96％）在其身体的至少一侧恢复了一种或多种神经功能水平，和7/22（32％）在其身体的至少一侧恢复了两个或更多个水平的神经功能。
LCTOPC1可以安全地用于宫颈SCI后亚急性期的参与者。注射程序,低剂量临时免疫抑制方案，和LCTOPC1耐受性良好。安全性和神经功能数据支持进一步研究以确定LCTOPC1治疗SCI的疗效。临床试验登记号.：NCT02302157（ClinicalTrials.gov）。
这项研究被设计为开放标签，剂量递增，多中心临床试验。25名C4-7美国脊髓损伤协会损伤量表A级或B级损伤的参与者接受了单剂量的2×106、1×107或2×107LCTOPC1，通过实质内注射到脊髓中使用定制设计的注射器定位装置。给予低剂量他克莫司直至第60天。结果测量包括不良事件(AE)监测和神经功能,如通过脊髓损伤的神经分类的国际标准测量的。
所有25名参与者至少经历了一次AE，在1年随访结束时,共报告了534例AE(32例研究相关与502例研究无关的SCI预期并发症).报告29例严重不良事件。两个3级严重不良事件（一个参与者的CSF泄漏和另一个参与者的细菌感染）被认为与注射程序和他克莫司的免疫抑制有关。分别。脑脊液渗漏有后遗症，包括自我限制的精神状态改变，感染通过抗生素治疗解决。对于所有参与者，核磁共振扫描没有显示肿块扩大的证据,与注射过程有关的脊髓损伤，脊髓的炎性病变，或心室系统中的肿块。在1年的随访中，意向治疗组的21/22（96％）在其身体的至少一侧恢复了一种或多种神经功能水平，和7/22（32％）在其身体的至少一侧恢复了两个或更多个水平的神经功能。
LCTOPC1可以安全地用于宫颈SCI后亚急性期的参与者。注射程序,低剂量临时免疫抑制方案，和LCTOPC1耐受性良好。安全性和神经功能数据支持进一步研究以确定LCTOPC1治疗SCI的疗效。临床试验登记号.：NCT02302157（ClinicalTrials.gov）。
