Stromal/stem cell implant improves motor function in patients with history of TBI
Patients with previous traumatic brain injury experienced significant improvement in motor functioning after implantation of mesenchymal stromal/stem cells, according to interim data from the STEMTRA phase 2 trial published in Neurology.
“Mesenchymal stromal/stem cell (MSC) implantation is a promising strategy for the treatment of TBI,” Masahito Kawabori, MD, PhD, of the department of neurosurgery at Hokkaido University Hospital in Sapporo, Japan, and colleagues wrote. “Allogeneic modified bone marrow-derived MSCs (SB623 cells, SanBio, Inc.) are in clinical development for chronic TBI and stroke without concomitant immunosuppressants which were determined to be unnecessary based on the prior Phase 1/2a clinical study and preclinical studies submitted to the FDA.”
Kawabori and colleagues conducted a 1-year, multicenter, double-blind, randomized, surgical sham-controlled trial of 61 patients (mean age, 34.4 years; men, 70.5%; median time since injury, 68.9 months) who were at least 12 months past the initial TBI. Patients had Glasgow Outcome Scale-Extended scores of 3 to 6 and focal cerebral injuries that were visible on MRI that correlated with chronic motor deficits. The mean Fugl-Meyer Motor Scale (FMMS) score at baseline was 52.2 in patients who received the SB623 implant and 52.3 in controls.
Researchers randomly assigned patients to receive either the SB623 implant (n = 46) or sham surgery (n = 15). The treatment group was further randomly assigned to 2.5x106 (n = 15), 5x106 (n = 15) or 10x106 (n = 16). They wrote that SB623 cells “are produced by the transient transfection of MSCs with a plasmid containing the human Notch-1 intracellular domain” and “increases [cells’] ability to secrete trophic factors, chemotactic factors and deposit extracellular matrix proteins which may support damaged neural cells.” The proprietary formulation is also being developed for other indications including spinal cord injury, according to SanBio.
Significant improvement of FMMS scores from baseline at 6 months served as the study’s primary endpoint. Researchers selected FMMS score, which is “well-established as a measure of motor impairment” and often used as a measurement of chronic stroke recovery, as the primary endpoint “because of its reliability and validity in measuring changes in patients with persistent motor deficits.”
FMSS scores improved more in patients treated with SB623 compared with controls at 6 months (least square [LS] mean, +8.3 vs. +2.3); the LS mean difference between scores was 6 (95% CI, 0.3-11.8). Patients in the 5.0x106 group saw the greatest FMMS score improvements at 6 months (+10.9 vs. +2.4 point improvement; P = .002) and had the highest percentage of patients whose FMMS scores improved by 10 or more points (53.3%).
No dose-limiting toxicities or deaths occurred. Treatment-emergent adverse events occurred in 100% of patients treated with SB623 compared with 93.3% of controls, though this difference was not statistically significant. Headache of mild or moderate severity was the most common treatment-emergent adverse event in both the SB623 pooled group (50%) and the control group (26.7%).
“In this interim analysis of a first double-blind, randomized, controlled clinical trial of cell therapy for chronic motor deficits secondary to TBI, treatment with SB623 cells appeared to be safe and was associated with statistically significant improvement of the Fugl-Meyer Motor Scale at 6 months,” the researchers wrote. “The favorable safety and efficacy outcomes reported here demonstrate the need for functional imaging studies and confirmatory Phase 3 clinical trials of SB623 cells for the treatment of chronic motor deficits secondary to TBI.”