Two-year safety and clinical outcomes in chronic ischemic stroke patients after implantation of modified bone marrow–derived mesenchymal stem cells (SB623): a phase 1/2a study

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OBJECTIVE

The aim of this study was to evaluate the safety and clinical outcomes associated with stereotactic surgical implantation of modified bone marrow–derived mesenchymal stem cells (SB623) in patients with stable chronic ischemic stroke.

METHODS

This was a 2-year, open-label, single-arm, phase 1/2a study; the selected patients had chronic motor deficits between 6 and 60 months after nonhemorrhagic stroke. SB623 cells were administered to the target sites surrounding the subcortical stroke region using MRI stereotactic image guidance.

RESULTS

A total of 18 patients were treated with SB623 cells. All experienced at least 1 treatment-emergent adverse event (TEAE). No patients withdrew due to adverse events, and there were no dose-limiting toxicities or deaths. The most frequent TEAE was headache related to the surgical procedure (88.9%). Seven patients experienced 9 serious adverse events, which resolved without sequelae. In 16 patients who completed 24 months of treatment, statistically significant improvements from baseline (mean) at 24 months were reported for the European Stroke Scale (ESS) score, 5.7 (95% CI 1.4–10.1, p < 0.05); National Institutes of Health Stroke Scale (NIHSS) score, −2.1 (95% CI −3.3 to −1.0, p < 0.01), Fugl-Meyer (F-M) total score, 19.4 (95% CI 9.9–29.0, p < 0.01); and F-M motor scale score, 10.4 (95% CI 4.0–16.7, p < 0.01). Measures of efficacy reached plateau by 12 months with no decline thereafter. There were no statistically significant changes in the modified Rankin Scale score. The size of transient lesions detected by T2-weighted FLAIR imaging in the ipsilateral cortex at weeks 1–2 postimplantation significantly correlated with improvement in ESS (0.619, p < 0.05) and NIHSS (−0.735, p < 0.01) scores at 24 months.

CONCLUSIONS

In this completed 2-year phase 1/2a study, implantation of SB623 cells in patients with stable chronic stroke was safe and was accompanied by improvements in clinical outcomes.

Clinical trial registration no.: NCT01287936 (clinicaltrials.gov)

ABBREVIATIONS ESS = European Stroke Scale; F-M = Fugl-Meyer; FMMS = Fugl-Meyer motor scale; HLA = human leukocyte antigen; mRS = modified Rankin Scale; NIHSS = National Institutes of Health Stroke Scale; PISCES = Pilot Investigation of Stem Cells in Stroke; SAE = serious adverse event; TEAE = treatment-emergent adverse event.

Article Information

Correspondence Gary Steinberg: Stanford University School of Medicine and Stanford Healthcare, Stanford, CA. cerebral@stanford.edu.

INCLUDE WHEN CITING Published online November 23, 2018; DOI: 10.3171/2018.5.JNS173147.

Disclosures This study was partly conducted at Stanford University School of Medicine and Stanford Health Care (SHC) and was funded by a contract with SanBio, Inc., which provided principal investigator, co-investigator, and coordinator fees. Dr. Steinberg and Dr. Schwartz are Stanford University School of Medicine employees. Dr. Steinberg is a consultant for Qool Therapeutics, Peter Lazic US, Inc., and NeuroSave.

This study was partly conducted at the University of Pittsburgh Medical School and University of Pittsburgh Medical Center (UPMC), and was funded by a contract with SanBio, Inc., which provided principal investigator and coordinator fees. Dr. Wechsler and Dr. Lunsford are employees of the University of Pittsburgh Medical School and UPMC. Dr. Kondziolka is a former employee of UPMC, and was a consultant for Elekta AB. Dr. Wechsler is a stockholder in Silk Road Medical and Remedy Pharm, is a consultant for Athersys and SanBio, Inc., and receives unrelated grant funding from Athersys, Inc. Dr. Lunsford is a consultant for and stockholder of Elekta AB and serves on the DSMB for Insightec. Personnel support for a principal investigator in this study was provided by the University of California, San Francisco, and was funded by a contract with SanBio, Inc. Dr. Kim is an employee of the University of California, San Francisco, and receives unrelated grant funding from BioGen Idec. Dr. Bates and Dr. McGrogan are full-time employees of SanBio, Inc. Dr. Poggio received consultancy fees from SanBio, Inc. and owns Biostatistical Consulting Inc., which provides statistical services to SanBio Inc. Dr. Case and Dr. Yankee are former employees and current stockholders of SanBio, Inc. Dr. Yankee is a consultant for SanBio, Inc. Dr. McGrogan is a stockholder of SanBio, Inc.

© AANS, except where prohibited by US copyright law.

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    Evaluation of clinical outcome endpoints at 24 months (intent-to-treat population, n = 18). A: ESS total score. B: NIHSS total score. C: F-M total score. D: FMMS total score. *p < 0.05, **p < 0.01, ***p < 0.001.

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    A: Time to first achievement of clinically meaningful improvement (n = 13). B: Mean F-M motor function total score change from baseline for patients who achieved (n = 13), and did not achieve clinically meaningful improvement (n = 5). C: Number of TEAEs (columns 1 and 2), number of TEAEs associated with cell treatment (columns 3 and 4), number of TEAEs associated with surgical procedure (columns 5 and 6), and number of SAEs (columns 7 and 8) at 0 to 1 year and > 1 to 2 years.

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