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

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

doi:10.1212/WNL.0000000000011450

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

Neurology. 2021 Feb 22;96(8):e1202-e1214. doi: 10.1212/WNL.0000000000011450.

Authors

Masahito Kawabori¹, Alan H Weintraub², Hideaki Imai², Iaroslav Zinkevych², Peter McAllister², Gary K Steinberg², Benjamin M Frishberg², Takao Yasuhara², Jefferson W Chen², Steven C Cramer², Achal S Achrol², Neil E Schwartz², Jun Suenaga², Daniel C Lu², Ihor Semeniv², Hajime Nakamura², Douglas Kondziolka², Dai Chida², Takehiko Kaneko², Yasuaki Karasawa², Susan Paadre², Bijan Nejadnik², Damien Bates², Anthony H Stonehouse², R Mark Richardson², David O Okonkwo²

Affiliations

¹ From the Department of Neurosurgery (M.K.), Hokkaido University Hospital, Sapporo, Japan; Rocky Mountain Regional Brain Injury System and University of Colorado School of Medicine (A.H.W.), Englewood; JCHO Tokyo Shinjuku Medical Center (H.I.), Japan; Ukraine Presidential Hospital (I.Z.), Kiev; New England Institute for Neurology and Headache (P.M.); New England Institute for Clinical Research (P.M.), Stamford; Department of Neurology (P.M.), Yale University, New Haven; Frank Netter School of Medicine (P.M.), Quinnipiac University, Hamden, CT; Department of Neurosurgery (G.K.S.), Department of Neurology and Neurological Sciences (N.E.S.), and Stanford Stroke Center (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; The Neurology Center of Southern California (B.M.F.), Carlsbad; Department of Neurological Surgery (T.Y.), Okayama University Graduate School of Medicine, Okayama University Hospital, Japan; Department of Neurological Surgery (J.W.C.), University of California, Irvine, School of Medicine; Department of Neurology (S.C.C.), University of California, Los Angeles; California Rehabilitation Institute (S.C.C.); Los Angeles; Department of Neurosurgery (A.S.A.), Loma Linda University Medical Center; Department of Neurosurgery (J.S.), Yokohama City University School of Medicine, Kanagawa, Japan; Department of Neurosurgery (D.C.L.), Ronald Reagan UCLA Medical Center, Los Angeles, CA; Clinical Hospital Feofaniya (I.S.), Kiev, Ukraine; Department of Neurosurgery (H.N.), Osaka University Graduate School of Medicine, Suita, Japan; Department of Neurosurgery (D.K.), New York University and NYU Langone Medical Center, NY; SanBio, Inc (D.C., T.K., B.N., D.B.), Mountain View, CA; Department of Neurosurgery (Y.K.), University of Tokyo Hospital, Japan; Biostatistical Consulting Inc (S.P.), Lexington, MA; Watson & Stonehouse Enterprises LLC (A.H.S.), Pacific Grove, CA; Massachusetts General Hospital and Harvard Medical School (R.M.R.), Boston; and Department of Neurological Surgery (D.O.O.), University of Pittsburgh Medical Center, PA. kawabori@med.hokudai.ac.jp.
² From the Department of Neurosurgery (M.K.), Hokkaido University Hospital, Sapporo, Japan; Rocky Mountain Regional Brain Injury System and University of Colorado School of Medicine (A.H.W.), Englewood; JCHO Tokyo Shinjuku Medical Center (H.I.), Japan; Ukraine Presidential Hospital (I.Z.), Kiev; New England Institute for Neurology and Headache (P.M.); New England Institute for Clinical Research (P.M.), Stamford; Department of Neurology (P.M.), Yale University, New Haven; Frank Netter School of Medicine (P.M.), Quinnipiac University, Hamden, CT; Department of Neurosurgery (G.K.S.), Department of Neurology and Neurological Sciences (N.E.S.), and Stanford Stroke Center (G.K.S., N.E.S.), Stanford University School of Medicine and Stanford Health Care, CA; The Neurology Center of Southern California (B.M.F.), Carlsbad; Department of Neurological Surgery (T.Y.), Okayama University Graduate School of Medicine, Okayama University Hospital, Japan; Department of Neurological Surgery (J.W.C.), University of California, Irvine, School of Medicine; Department of Neurology (S.C.C.), University of California, Los Angeles; California Rehabilitation Institute (S.C.C.); Los Angeles; Department of Neurosurgery (A.S.A.), Loma Linda University Medical Center; Department of Neurosurgery (J.S.), Yokohama City University School of Medicine, Kanagawa, Japan; Department of Neurosurgery (D.C.L.), Ronald Reagan UCLA Medical Center, Los Angeles, CA; Clinical Hospital Feofaniya (I.S.), Kiev, Ukraine; Department of Neurosurgery (H.N.), Osaka University Graduate School of Medicine, Suita, Japan; Department of Neurosurgery (D.K.), New York University and NYU Langone Medical Center, NY; SanBio, Inc (D.C., T.K., B.N., D.B.), Mountain View, CA; Department of Neurosurgery (Y.K.), University of Tokyo Hospital, Japan; Biostatistical Consulting Inc (S.P.), Lexington, MA; Watson & Stonehouse Enterprises LLC (A.H.S.), Pacific Grove, CA; Massachusetts General Hospital and Harvard Medical School (R.M.R.), Boston; and Department of Neurological Surgery (D.O.O.), University of Pittsburgh Medical Center, PA.

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.

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Associated data

ClinicalTrials.gov/NCT02416492