Volume 2, Issue 1, March 2018, Page: 1-8
SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study
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
Received: Oct. 26, 2017;       Accepted: Nov. 8, 2017;       Published: Dec. 23, 2017
DOI: 10.11648/j.cnn.20180201.11      View  1292      Downloads  68
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).
Keywords
SUN13837, Spinal Cord Injury, Neuroprotection, bFGF
To cite this article
Benjamin Levinson, James Lee, Hubert Chou, Dennis Maiman, SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study, Clinical Neurology and Neuroscience. Vol. 2, No. 1, 2018, pp. 1-8. doi: 10.11648/j.cnn.20180201.11
Copyright
Copyright © 2017 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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