SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study

Benjamin Levinson; James Lee; Hubert Chou; Dennis Maiman

doi:doi:10.11648/j.cnn.20180201.11

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SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study

Benjamin Levinson, James Lee, Hubert Chou, Dennis Maiman

Published in Clinical Neurology and Neuroscience (Volume 2, Issue 1)

Received: 26 October 2017 Accepted: 8 November 2017 Published: 23 December 2017

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Abstract

The purpose of this study was to assess the safety and efficacy of SUN13837, a bFGF mimetic, for the treatment of acute cervical spinal cord injury. In a 26-week, double-blind trial, 65 subjects were randomized (1:1) by stratum within 12 hours of injury to 1 mg/kg/day of intravenous SUN13837 (SUN) or matching placebo (pbo) for no less than 7 and no more 28 days. The efficacy measures at Week 16 were the mean total SCIM III (primary), combined SCIM III Self-Care and Mobility subscales (secondary) and ISNCSCI Total Motor scores (secondary). Of the 61 subjects who received study drug, 57 received at least 7 doses. 55 subjects (ITT population) were assessed by treatment assignment and by strata of C4-C5 AIS A (pbo=13, SUN=15), C6-C7 AIS A (pbo=6, SUN=5) or C3-C8 AIS B and C (pbo=9, SUN=7). The majority of subjects were Male (85.2%), Caucasian (63.9%). The Total SCIM III score between the 2 treatment groups at Week 16 was 4.54 (SE = 6.524), not statistically significant with p = 0.4912. Therefore, the primary end-point was not reached. Overall, larger effects were observed in AIS C6-C7 and AIS B and C strata as compared with AIS A C4-C5. Specifically, in the C3-8 AIS B and C stratum, a 6.8-point difference (LS) in Total SCIM III was observed (SUN vs. pbo). However, there were more AIS C subjects in the SUN (n=5) vs. pbo (n=2). The combination of self-care and mobility scores was not statistically significant with p-value = 0.3951. By Week 16, the LS Mean (SE) change from baseline in UEMS scores was 9.92 in SUN13837-treated subjects compared to 4.95 in Placebo-treated subjects (p-value = 0.0347). The largest treatment difference was seen in the AIS B and C strata in which SUN13837-treated subjects had an average change from baseline in UEMS of 25.40 compared to 6.86 in Placebo-treated subjects. As a result, the AIS B and C stratum may have contributed heavily to the overall treatment effect on the UEMS with lesser contribution by AIS A C4-C5 and C6-C7 strata. Analyses of primary and secondary outcomes showed non-significant trends consistently favoring SUN13837 treatment. The efficacy signal of SUN13837 warrants further investigation. No safety concerns were noted by an Independent Data Safety Monitoring and Review Board. Pharmacokinetic modeling indicates that the dose may need to be lowered in any further evaluation of SUN13837 (NCT01502631).

Published in	Clinical Neurology and Neuroscience (Volume 2, Issue 1)
DOI	10.11648/j.cnn.20180201.11
Page(s)	1-8
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2017. Published by Science Publishing Group

Keywords

SUN13837, Spinal Cord Injury, Neuroprotection, bFGF

References

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[2]	Wyndaele M, Wyndaele, JJ. Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey? Spinal Cord. 2006 Sep; 44 (9): 523-9.
[3]	Berkowitz M. The costs of spinal cord injury. In: Lin V, ed in chief; Cardenas D, Cutter N, Frost F, Hammond M, Lindblom LB, Perkash I, et al, eds. Spinal Cord Medicine Principles and Practice. New York, NY: Demos Medical Publishing, Inc.; 2003:949-55.
[4]	Bosshart HT. Social issues in spinal cord injury. In: Lin V, ed-in chief; Cardenas D, Cutter N, Frost F, Hammond M, Lindblom LB, Perkash I, et al, eds. Spinal Cord Medicine Principles and Practice. New York, NY: Demos Medical Publishing, Inc.; 2003:941-8.
[5]	Rabchevsky AG, Fugaccia I, Turner AF, Blades DA, Mattson MP, Scheff SW. Basic fibroblast growth factor (bFGF) enhances functional recovery following severe spinal cord injury to the rat. Exp Neurol. 2000 Aug; 164 (2): 280-91.
[6]	Song BW, Vinters HV, Wu D, and Pardridge WM. Enhanced neuroprotective effects of basic fibroblast growth ractor in regional brain ischemia after conjugation to a blood brain barrier delivery vector. J Pharmacol Exp Ther. 2002 May; 301 (2): 605-10.
[7]	Bossard C, Laurell H, Van den Berghe L, Meunier S, Zanibellato C, Prats H. Translokin is an intracellular mediator of FGF 2 trafficking. Nat Cell Biol. 2003 May; 5 (5): 433 9.
[8]	Steeves JD, Lammertse D, Curt A, Fawcett JW, Tuszynski MH, Ditunno JF, et al. Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures. Spinal Cord. 2007 Mar; 45 (3): 206-21. Epub 2006 Dec 19.
[9]	http://www.asia-spinalinjury.org/elearning/ISNCSCI.php.
[10]	Scivoletto G, Tamburella F, Laurenza L, Molinari M. The spinal cord independence measure: how much change is clinically significant for spinal cord injury subjects. Disabil Rehabil, 2013 Oct; 35 (21): 1808–13.
[11]	Lammertse D, et al., oral communication, Feb 2016.
[12]	Fawcett JW, Curt A, Steeves JD, Coleman WP, Tuszynski MH, Lammertse D, et al. Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials. Spinal Cord. 2007 Mar; 45 (3): 190-205. Epub 2006 Dec.
[13]	Report from the Institute of Medicine: Spinal cord injury: progress, promise, and priorities / Committee on Spinal Cord Injury, Board on Neuroscience and Behavioral Health; Catharyn T. Liverman, et al., Editors. National Academies Press, 500 Fifth Street, N. W., Lockbox 285, Washington, DC 20055; 2005 p 32.
[14]	Kiwerski J. The natural history of neurological recovery in patients with traumatic tetraplegia Paraplegia. 1989 Feb; 27 (1): 41-5.
[15]	McKinley W, Pai AB, and Kulkarni U. Functional Outcomes per Level of Spinal Cord Injury. 2015-Jul-15. Retrieved from: http://emedicine.medscape.com/article/322604-overview.
[16]	Rudhe C, van Hedel HJ. Upper extremity function in persons with tetraplegia: relationships between strength, capacity, and the spinal cord independence measure. Neurorehabil Neural Repair. 2009 Jun; 23 (5): 413-21.

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APA Style

Benjamin Levinson, James Lee, Hubert Chou, Dennis Maiman. (2017). SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study. Clinical Neurology and Neuroscience, 2(1), 1-8. https://doi.org/10.11648/j.cnn.20180201.11

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ACS Style

Benjamin Levinson; James Lee; Hubert Chou; Dennis Maiman. SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study. Clin. Neurol. Neurosci. 2017, 2(1), 1-8. doi: 10.11648/j.cnn.20180201.11

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AMA Style

Benjamin Levinson, James Lee, Hubert Chou, Dennis Maiman. SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study. Clin Neurol Neurosci. 2017;2(1):1-8. doi: 10.11648/j.cnn.20180201.11

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@article{10.11648/j.cnn.20180201.11,
  author = {Benjamin Levinson and James Lee and Hubert Chou and Dennis Maiman},
  title = {SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study},
  journal = {Clinical Neurology and Neuroscience},
  volume = {2},
  number = {1},
  pages = {1-8},
  doi = {10.11648/j.cnn.20180201.11},
  url = {https://doi.org/10.11648/j.cnn.20180201.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cnn.20180201.11},
  abstract = {The purpose of this study was to assess the safety and efficacy of SUN13837, a bFGF mimetic, for the treatment of acute cervical spinal cord injury. In a 26-week, double-blind trial, 65 subjects were randomized (1:1) by stratum within 12 hours of injury to 1 mg/kg/day of intravenous SUN13837 (SUN) or matching placebo (pbo) for no less than 7 and no more 28 days. The efficacy measures at Week 16 were the mean total SCIM III (primary), combined SCIM III Self-Care and Mobility subscales (secondary) and ISNCSCI Total Motor scores (secondary). Of the 61 subjects who received study drug, 57 received at least 7 doses. 55 subjects (ITT population) were assessed by treatment assignment and by strata of C4-C5 AIS A (pbo=13, SUN=15), C6-C7 AIS A (pbo=6, SUN=5) or C3-C8 AIS B and C (pbo=9, SUN=7). The majority of subjects were Male (85.2%), Caucasian (63.9%). The Total SCIM III score between the 2 treatment groups at Week 16 was 4.54 (SE = 6.524), not statistically significant with p = 0.4912. Therefore, the primary end-point was not reached. Overall, larger effects were observed in AIS C6-C7 and AIS B and C strata as compared with AIS A C4-C5. Specifically, in the C3-8 AIS B and C stratum, a 6.8-point difference (LS) in Total SCIM III was observed (SUN vs. pbo). However, there were more AIS C subjects in the SUN (n=5) vs. pbo (n=2). The combination of self-care and mobility scores was not statistically significant with p-value = 0.3951. By Week 16, the LS Mean (SE) change from baseline in UEMS scores was 9.92 in SUN13837-treated subjects compared to 4.95 in Placebo-treated subjects (p-value = 0.0347). The largest treatment difference was seen in the AIS B and C strata in which SUN13837-treated subjects had an average change from baseline in UEMS of 25.40 compared to 6.86 in Placebo-treated subjects. As a result, the AIS B and C stratum may have contributed heavily to the overall treatment effect on the UEMS with lesser contribution by AIS A C4-C5 and C6-C7 strata. Analyses of primary and secondary outcomes showed non-significant trends consistently favoring SUN13837 treatment. The efficacy signal of SUN13837 warrants further investigation. No safety concerns were noted by an Independent Data Safety Monitoring and Review Board. Pharmacokinetic modeling indicates that the dose may need to be lowered in any further evaluation of SUN13837 (NCT01502631).},
 year = {2017}
}

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TY  - JOUR
T1  - SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study
AU  - Benjamin Levinson
AU  - James Lee
AU  - Hubert Chou
AU  - Dennis Maiman
Y1  - 2017/12/23
PY  - 2017
N1  - https://doi.org/10.11648/j.cnn.20180201.11
DO  - 10.11648/j.cnn.20180201.11
T2  - Clinical Neurology and Neuroscience
JF  - Clinical Neurology and Neuroscience
JO  - Clinical Neurology and Neuroscience
SP  - 1
EP  - 8
PB  - Science Publishing Group
SN  - 2578-8930
UR  - https://doi.org/10.11648/j.cnn.20180201.11
AB  - The purpose of this study was to assess the safety and efficacy of SUN13837, a bFGF mimetic, for the treatment of acute cervical spinal cord injury. In a 26-week, double-blind trial, 65 subjects were randomized (1:1) by stratum within 12 hours of injury to 1 mg/kg/day of intravenous SUN13837 (SUN) or matching placebo (pbo) for no less than 7 and no more 28 days. The efficacy measures at Week 16 were the mean total SCIM III (primary), combined SCIM III Self-Care and Mobility subscales (secondary) and ISNCSCI Total Motor scores (secondary). Of the 61 subjects who received study drug, 57 received at least 7 doses. 55 subjects (ITT population) were assessed by treatment assignment and by strata of C4-C5 AIS A (pbo=13, SUN=15), C6-C7 AIS A (pbo=6, SUN=5) or C3-C8 AIS B and C (pbo=9, SUN=7). The majority of subjects were Male (85.2%), Caucasian (63.9%). The Total SCIM III score between the 2 treatment groups at Week 16 was 4.54 (SE = 6.524), not statistically significant with p = 0.4912. Therefore, the primary end-point was not reached. Overall, larger effects were observed in AIS C6-C7 and AIS B and C strata as compared with AIS A C4-C5. Specifically, in the C3-8 AIS B and C stratum, a 6.8-point difference (LS) in Total SCIM III was observed (SUN vs. pbo). However, there were more AIS C subjects in the SUN (n=5) vs. pbo (n=2). The combination of self-care and mobility scores was not statistically significant with p-value = 0.3951. By Week 16, the LS Mean (SE) change from baseline in UEMS scores was 9.92 in SUN13837-treated subjects compared to 4.95 in Placebo-treated subjects (p-value = 0.0347). The largest treatment difference was seen in the AIS B and C strata in which SUN13837-treated subjects had an average change from baseline in UEMS of 25.40 compared to 6.86 in Placebo-treated subjects. As a result, the AIS B and C stratum may have contributed heavily to the overall treatment effect on the UEMS with lesser contribution by AIS A C4-C5 and C6-C7 strata. Analyses of primary and secondary outcomes showed non-significant trends consistently favoring SUN13837 treatment. The efficacy signal of SUN13837 warrants further investigation. No safety concerns were noted by an Independent Data Safety Monitoring and Review Board. Pharmacokinetic modeling indicates that the dose may need to be lowered in any further evaluation of SUN13837 (NCT01502631).
VL  - 2
IS  - 1
ER  -

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Author Information

Benjamin Levinson

Department of Clinical Research, Daiichi-Sankyo Pharma Development, Basking Ridge, USA
James Lee

Department of Clinical Research, Daiichi-Sankyo Pharma Development, Basking Ridge, USA
Hubert Chou

Department of Clinical Research, Daiichi-Sankyo Pharma Development, Basking Ridge, USA
Dennis Maiman

Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, USA

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APA Style

Benjamin Levinson, James Lee, Hubert Chou, Dennis Maiman. (2017). SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study. Clinical Neurology and Neuroscience, 2(1), 1-8. https://doi.org/10.11648/j.cnn.20180201.11

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ACS Style

Benjamin Levinson; James Lee; Hubert Chou; Dennis Maiman. SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study. Clin. Neurol. Neurosci. 2017, 2(1), 1-8. doi: 10.11648/j.cnn.20180201.11

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AMA Style

Benjamin Levinson, James Lee, Hubert Chou, Dennis Maiman. SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study. Clin Neurol Neurosci. 2017;2(1):1-8. doi: 10.11648/j.cnn.20180201.11

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@article{10.11648/j.cnn.20180201.11,
  author = {Benjamin Levinson and James Lee and Hubert Chou and Dennis Maiman},
  title = {SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study},
  journal = {Clinical Neurology and Neuroscience},
  volume = {2},
  number = {1},
  pages = {1-8},
  doi = {10.11648/j.cnn.20180201.11},
  url = {https://doi.org/10.11648/j.cnn.20180201.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cnn.20180201.11},
  abstract = {The purpose of this study was to assess the safety and efficacy of SUN13837, a bFGF mimetic, for the treatment of acute cervical spinal cord injury. In a 26-week, double-blind trial, 65 subjects were randomized (1:1) by stratum within 12 hours of injury to 1 mg/kg/day of intravenous SUN13837 (SUN) or matching placebo (pbo) for no less than 7 and no more 28 days. The efficacy measures at Week 16 were the mean total SCIM III (primary), combined SCIM III Self-Care and Mobility subscales (secondary) and ISNCSCI Total Motor scores (secondary). Of the 61 subjects who received study drug, 57 received at least 7 doses. 55 subjects (ITT population) were assessed by treatment assignment and by strata of C4-C5 AIS A (pbo=13, SUN=15), C6-C7 AIS A (pbo=6, SUN=5) or C3-C8 AIS B and C (pbo=9, SUN=7). The majority of subjects were Male (85.2%), Caucasian (63.9%). The Total SCIM III score between the 2 treatment groups at Week 16 was 4.54 (SE = 6.524), not statistically significant with p = 0.4912. Therefore, the primary end-point was not reached. Overall, larger effects were observed in AIS C6-C7 and AIS B and C strata as compared with AIS A C4-C5. Specifically, in the C3-8 AIS B and C stratum, a 6.8-point difference (LS) in Total SCIM III was observed (SUN vs. pbo). However, there were more AIS C subjects in the SUN (n=5) vs. pbo (n=2). The combination of self-care and mobility scores was not statistically significant with p-value = 0.3951. By Week 16, the LS Mean (SE) change from baseline in UEMS scores was 9.92 in SUN13837-treated subjects compared to 4.95 in Placebo-treated subjects (p-value = 0.0347). The largest treatment difference was seen in the AIS B and C strata in which SUN13837-treated subjects had an average change from baseline in UEMS of 25.40 compared to 6.86 in Placebo-treated subjects. As a result, the AIS B and C stratum may have contributed heavily to the overall treatment effect on the UEMS with lesser contribution by AIS A C4-C5 and C6-C7 strata. Analyses of primary and secondary outcomes showed non-significant trends consistently favoring SUN13837 treatment. The efficacy signal of SUN13837 warrants further investigation. No safety concerns were noted by an Independent Data Safety Monitoring and Review Board. Pharmacokinetic modeling indicates that the dose may need to be lowered in any further evaluation of SUN13837 (NCT01502631).},
 year = {2017}
}

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TY  - JOUR
T1  - SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study
AU  - Benjamin Levinson
AU  - James Lee
AU  - Hubert Chou
AU  - Dennis Maiman
Y1  - 2017/12/23
PY  - 2017
N1  - https://doi.org/10.11648/j.cnn.20180201.11
DO  - 10.11648/j.cnn.20180201.11
T2  - Clinical Neurology and Neuroscience
JF  - Clinical Neurology and Neuroscience
JO  - Clinical Neurology and Neuroscience
SP  - 1
EP  - 8
PB  - Science Publishing Group
SN  - 2578-8930
UR  - https://doi.org/10.11648/j.cnn.20180201.11
AB  - The purpose of this study was to assess the safety and efficacy of SUN13837, a bFGF mimetic, for the treatment of acute cervical spinal cord injury. In a 26-week, double-blind trial, 65 subjects were randomized (1:1) by stratum within 12 hours of injury to 1 mg/kg/day of intravenous SUN13837 (SUN) or matching placebo (pbo) for no less than 7 and no more 28 days. The efficacy measures at Week 16 were the mean total SCIM III (primary), combined SCIM III Self-Care and Mobility subscales (secondary) and ISNCSCI Total Motor scores (secondary). Of the 61 subjects who received study drug, 57 received at least 7 doses. 55 subjects (ITT population) were assessed by treatment assignment and by strata of C4-C5 AIS A (pbo=13, SUN=15), C6-C7 AIS A (pbo=6, SUN=5) or C3-C8 AIS B and C (pbo=9, SUN=7). The majority of subjects were Male (85.2%), Caucasian (63.9%). The Total SCIM III score between the 2 treatment groups at Week 16 was 4.54 (SE = 6.524), not statistically significant with p = 0.4912. Therefore, the primary end-point was not reached. Overall, larger effects were observed in AIS C6-C7 and AIS B and C strata as compared with AIS A C4-C5. Specifically, in the C3-8 AIS B and C stratum, a 6.8-point difference (LS) in Total SCIM III was observed (SUN vs. pbo). However, there were more AIS C subjects in the SUN (n=5) vs. pbo (n=2). The combination of self-care and mobility scores was not statistically significant with p-value = 0.3951. By Week 16, the LS Mean (SE) change from baseline in UEMS scores was 9.92 in SUN13837-treated subjects compared to 4.95 in Placebo-treated subjects (p-value = 0.0347). The largest treatment difference was seen in the AIS B and C strata in which SUN13837-treated subjects had an average change from baseline in UEMS of 25.40 compared to 6.86 in Placebo-treated subjects. As a result, the AIS B and C stratum may have contributed heavily to the overall treatment effect on the UEMS with lesser contribution by AIS A C4-C5 and C6-C7 strata. Analyses of primary and secondary outcomes showed non-significant trends consistently favoring SUN13837 treatment. The efficacy signal of SUN13837 warrants further investigation. No safety concerns were noted by an Independent Data Safety Monitoring and Review Board. Pharmacokinetic modeling indicates that the dose may need to be lowered in any further evaluation of SUN13837 (NCT01502631).
VL  - 2
IS  - 1
ER  -

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