Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2021 Feb 22;96(8):e1202-e1214.
doi: 10.1212/WNL.0000000000011450.

Cell Therapy for Chronic TBI: Interim Analysis of the Randomized Controlled STEMTRA Trial

Masahito Kawabori  1 , Alan H Weintraub  2 , Hideaki Imai  2 , Iaroslav Zinkevych  2 , Peter McAllister  2 , Gary K Steinberg  2 , Benjamin M Frishberg  2 , Takao Yasuhara  2 , Jefferson W Chen  2 , Steven C Cramer  2 , Achal S Achrol  2 , Neil E Schwartz  2 , Jun Suenaga  2 , Daniel C Lu  2 , Ihor Semeniv  2 , Hajime Nakamura  2 , Douglas Kondziolka  2 , Dai Chida  2 , Takehiko Kaneko  2 , Yasuaki Karasawa  2 , Susan Paadre  2 , Bijan Nejadnik  2 , Damien Bates  2 , Anthony H Stonehouse  2 , R Mark Richardson  2 , David O Okonkwo  2
Affiliations
Comment

Cell Therapy for Chronic TBI: Interim Analysis of the Randomized Controlled STEMTRA Trial

Masahito Kawabori et al. Neurology. .

Abstract

Objective: To determine whether chronic motor deficits secondary to traumatic brain injury (TBI) can be improved by implantation of allogeneic modified bone marrow-derived mesenchymal stromal/stem cells (SB623).

Methods: This 6-month interim analysis of the 1-year double-blind, randomized, surgical sham-controlled, phase 2 Stem Cell Therapy for Traumatic Brain Injury (STEMTRA) trial (NCT02416492) evaluated safety and efficacy of the stereotactic intracranial implantation of SB623 in patients with stable chronic motor deficits secondary to TBI. Patients in this multicenter trial (n = 63) underwent randomization in a 1:1:1:1 ratio to 2.5 × 106, 5.0 × 106, or 10 × 106 SB623 cells or control. Safety was assessed in patients who underwent surgery (n = 61), and efficacy was assessed in the modified intent-to-treat population of randomized patients who underwent surgery (n = 61; SB623 = 46, control = 15).

Results: The primary efficacy endpoint of significant improvement from baseline of Fugl-Meyer Motor Scale score at 6 months for SB623-treated patients was achieved. SB623-treated patients improved by (least square [LS] mean) 8.3 (standard error 1.4) vs 2.3 (standard error 2.5) for control at 6 months, the LS mean difference was 6.0 (95% confidence interval 0.3-11.8, p = 0.040). Secondary efficacy endpoints improved from baseline but were not statistically significant vs control at 6 months. There were no dose-limiting toxicities or deaths, and 100% of SB623-treated patients experienced treatment-emergent adverse events vs 93.3% of control patients (p = 0.25).

Conclusions: SB623 cell implantation appeared to be safe and well tolerated, and patients implanted with SB623 experienced significant improvement from baseline motor status at 6 months compared to controls.

Clinicaltrialsgov identifier: NCT02416492.

Classification of evidence: This study provides Class I evidence that implantation of SB623 was well tolerated and associated with improvement in motor status.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Consort Diagram
Intent-to-treat (ITT) population (n = 63): patients randomized to SB623 cell treatment or sham surgery. Modified ITT (mITT) population (n = 61): patients randomized to SB623 treatment or sham surgery, minus 2 patients, 1 each from the SB623 2.5 × 106 and 5.0 × 106 treatment groups who discontinued before treatment because physicians could not determine safe cell injection trajectories. Safety population (n = 61): patients who enrolled and underwent SB623 treatment or sham surgery.
Figure 2
Figure 2. Primary Efficacy Endpoint Measures
(A) Fugl-Meyer Motor Scale (FMMS) score change from baseline for SB623 pooled and sham control groups at time points up to 6 months (modified intent-to-treat [mITT] population, n = 61). *p < 0.05. (B) Percent of patients in each treatment group who achieved potentially clinically meaningful improvement of FMMS score (≥10 points) at 6 months (mITT population, n = 61). *p < 0.05. (C) FMMS dose response: change from baseline for each treatment group at time points up to 6 months (mITT population, n = 61). Difference found between the 5.0 × 106 treatment and sham surgery groups was calculated separately and did not include comparisons between other SB623 treatment groups and the sham surgery group. **p < 0.01.
See this image and copyright information in PMC

Comment in

Comment on

References

    1. James SL, Theadom A, Ellenbogen RG; GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019;18:56–87. - PMC - PubMed
    1. Selassie AW, Zaloshnja E, Langlois JA, Miller T, Jones P, Steiner C. Incidence of long-term disability following traumatic brain injury hospitalization, United States, 2003. J Head Trauma Rehabil 2008;23:123–131. - PubMed
    1. Thurman DJ, Alverson C, Dunn KA, Guerrero J, Sniezek JE. Traumatic brain injury in the United States: a public health perspective. J Head Trauma Rehabil 1999;14:602–615. - PubMed
    1. Walker WC, Pickett TC. Motor impairment after severe traumatic brain injury: a longitudinal multicenter study. J Rehabil Res Dev 2007;44:975–982. - PubMed
    1. Seledtsov VI, Rabinovich SS, Parlyuk OV, et al. . Cell transplantation therapy in re-animating severely head-injured patients. Biomed Pharmacother 2005;59:415–420. - PubMed

Associated data