There was no statistically significant difference between treatment-related adverse events in the SB623 stem cell and control groups.
Data from the 1-year double-blind, randomized, surgical sham-controlled, phase 2 STEMTRA trial (NCT02416492) suggests that implantation of allogeneic modified bone marrow-derived mesenchymal stromal/stem cells (MSCs), dubbed SB623 and developed by SanBio, is well-tolerated and efficacious in treating traumatic brain injury (TBI).
Patients treated with SB623 improved by a least squares (LS) mean of 8.3 (standard error [SE], 1.4) at 6 months from baseline on the Fugl-Meyer Motor Scale (FMSS) score compared to an LS mean improvement of 2.3 (SE, 2.5) in the control group. The LS mean difference was 6.0 (95% CI, 0.3–1.8; P = .04) between SB623 and control.
Principal author Masahito Kawabori, MD, PhD, associate professor, Department of Neuronal Cell Therapy, Hokkaido University, and colleagues wrote that “MSC implantation is a promising strategy for the treatment of TBI. Early-stage clinical studies of several cell types implanted during the acute-to-chronic phases of TBI have shown favorable results. Allogeneic modified bone marrow-derived MSCs are in clinical development for chronic TBI and stroke.”
Kawabori and colleagues enrolled 63 patients into the study, 15 patients in the control group and 16 in each of the 3 SB623 groups that were treated with either 2.5x106, 5.0x106, or 10x106 SB623 cells.
A clinically meaningful improvement of ≥10 points on FMSS was reached in 39.1% of the SB623 pooled group versus 6.7% of controls (P = .039). Of these SB623 patients, 53.3% received 5.0x106 SB623 cells. The 5.0x106 group showed greater improvement on FMMS at 3 months, but there was no relationship between cell dose and FMMS score change at 6 months (P = .82).
Secondary efficacy end points improved from baseline but were not statistically significant compared with the control group at 6 months. These include changes from baseline on disability rating scale, gait velocity, Quality of Life in Neurological Disorders lower extremity function T score, and Global Rating of Perceived Change.
Kawabori and colleagues also genotyped patients but found that there were no relationships between FMMS change from baseline and at least 1 Met allele of brain-derived neurotrophic factor or at least 1 APOE4 allele. There were also no differences in daily activity count change from baseline between SB623 pooled and control groups for the affected (P = .25) and non-affected (P = .96) sides of the body at 6 months.
All SB623 patients experienced treatment-emergent adverse events (TEAEs) as compared to 93.3% of control patients (P = .25). Headache was the most frequent TEAE, with 50% of the SB623 group and 26.7% of the control group reporting this mild-to-moderate TEAE (P = .14). Most headaches initiated between days 1–3 after procedure and lasted until day 28 after the procedure. Pyrexia occurred in 6 patients in the SB623 group, 4 of which initiated on day 3. In the 17 patients with parenchymal or subdural hematoma in the SB623 group, 47% (n = 8) experienced headache as compared to 50% of the control group.
Two patients, 1 each in the SB623 2.5x106 and 5.0x106 treated groups, discontinued prior to cell treatment, as physicians could not determine safe stereotactic injection trajectories. In total, out of the 46 patients in the SB623 pooled group, there were 223 TEAEs, 98.2% of which were mild-moderate intensity, as compared to 65 TEAEs in the control group of 15 patients, 93.8% of which were mild-to-moderate intensity. No dose-limiting toxicities or deaths occurred.
Kawabori and colleagues classified 92% of TEAEs in all patients as unrelated or unlikely to be related to cell treatment. They did not classify any TEAEs as definitely related to cell treatment and classified 2 (0.9%; headache and hemiparesis) as probably related to cell treatment in the SB623 pooled group. Serious TEAEs occurred in 4 (8.7%) SB623-treated patients versus 2 (13.3%) control patients.
“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,” Kawabori and colleagues concluded.