Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of SUN13837 Injection in Adult Subjects With Acute Spinal Cord Injury (ASCI)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of SUN13837 Injection in Adult Subjects With Acute Spinal Cord Injury

The purpose of this research study is to gather scientific information about the effectiveness of the study drug, SUN13837 Injection, when compared with the placebo (inactive substance) in participants with acute spinal cord injury.

Study Overview

• Status: Completed
• Conditions: Acute Spinal Cord Injury
• Intervention / Treatment: Drug: SUN13837 injection; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H3A7
  • Ontario
    • Hamilton, Ontario, Canada, L8L2X2
    • Toronto, Ontario, Canada, M5C 1R6
    • Toronto, Ontario, Canada, M4G 3V9
    • Toronto, Ontario, Canada, M4G3V9
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
• Czechia
  • Brno, Czechia, 625 00
  • Liberec 1, Czechia, 460 63
  • Ostrava, Czechia, 708 52
  • Prague 5, Czechia, 150 06
• France
  • Amiens Cedex, France, 80054
  • Berck, France, 62608
  • Bordeaux, France, 33076
  • Bordeaux, France, 33523
  • Lille Cedex, France, 59037
  • Montpellier, France, 34295
  • Montpellier, France, 34090
• Poland
  • Lodz, Poland, 93-513
  • Sosnowiec, Poland, 41-200
• Spain
  • Barcelona, Spain, 08035
  • Barcelona, Spain, 08916
  • Barcelona, Spain, 08316
  • La Coruña, Spain, 15670
  • Sevilla, Spain, 41013
• United Kingdom
  • Middlesborough, United Kingdom, TS4 3BW
  • Birmingham
    • Edgbaston, Birmingham, United Kingdom, B15 2WB
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0BQ
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
  • California
    • Downey, California, United States, 90242
    • Los Angeles, California, United States, 90033
    • Sacramento, California, United States, 95817
    • San Jose, California, United States, 95128
  • Colorado
    • Denver, Colorado, United States, 80204
    • Englewood, Colorado, United States, 80113
  • Delaware
    • Newark, Delaware, United States, 19718
  • Florida
    • Hollywood, Florida, United States, 33021
  • Georgia
    • Atlanta, Georgia, United States, 30322
    • Atlanta, Georgia, United States, 30309
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
  • Indiana
    • Indianapolis, Indiana, United States, 67214
  • Iowa
    • Davenport, Iowa, United States, 52804
    • Iowa City, Iowa, United States, 52242
  • Kansas
    • Kansas City, Kansas, United States, 66160
  • Kentucky
    • Lexington, Kentucky, United States, 40536
    • Lexington, Kentucky, United States, 40504
  • Missouri
    • Columbia, Missouri, United States, 65212
    • Columbia, Missouri, United States, 65203
    • Kansas City, Missouri, United States, 64108
    • Springfield, Missouri, United States, 65807
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
    • Omaha, Nebraska, United States, 68122
    • Omaha, Nebraska, United States, 68198-2035
  • New Jersey
    • Camden, New Jersey, United States, 08103
    • Newark, New Jersey, United States, 07103
    • West Orange, New Jersey, United States, 07052
  • New York
    • Great Neck, New York, United States, 11021
    • Stony Brook, New York, United States, 11794-8122
    • Valhalla, New York, United States, 10595
    • White Plains, New York, United States, 10605
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
    • Winston-Salem, North Carolina, United States, 27157
  • Ohio
    • Cleveland, Ohio, United States, 44109
    • Dayton, Ohio, United States, 45409
  • Pennsylvania
    • Malvern, Pennsylvania, United States, 19355
    • Philadelphia, Pennsylvania, United States, 19140
    • Philadelphia, Pennsylvania, United States, 19102
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Acute traumatic injury to the cervical neurological spinal cord as follows:

   1. American Spinal Injury Association Impairment Scale A (AIS A) with a level of injury at either cervical level C4, C5, C6, C7 (for C4, the participant must have at least 1 point of motor activity within the zone of partial preservation (ZPP) inclusive of C5 to thoracic level 1 [T1]). In addition, the AIS A participant may be included if ALL of the following are present 1) the most caudal intact sensory segment (both pinprick and light touch) is C3, 2) at least one side (right or left) has both intact pinprick and light touch sensation in the C4 dermatome, AND 3) at least 1 point of motor activity within the ZPP inclusive of C5 to T1
   2. American Spinal Injury Association Impairment Scale B or C (AIS B or C) with a neurological level of injury at either C3, C4, C5, C6, C7, or C8 AND a total LEMS of 5 or fewer motor points
2. Closed single traumatic spinal cord injury occurring within 12 hours of first dosing
3. Male or female cervical AIS A participants ≥ 16 to ≤ 80 years and male or female cervical AIS B or C participants ≥16 to ≤70 years
4. Females of childbearing potential and males must agree to maintain adequate contraception for the first 35 days of the study

Exclusion Criteria:

1. Unable to obtain informed consent (either from the participant or from the participant's legally authorized representative [LAR])
2. Women who are breastfeeding (if unwilling to stop for the first 35 days of the study) or who are pregnant
3. Coma or significant impairment in the level of consciousness that interferes with the performance or interpretation of protocol specified assessments
4. Any disease, concomitant injury, or condition that interferes with the performance or interpretation of the protocol specified assessments
5. Unable, as determined by the investigator, or unwilling to discontinue use of potent P-glycoprotein (P-gp) inhibitors for the first 35 days of the study
6. Unable, as determined by the investigator, or unwilling to discontinue use of potent cytochrome P450 (CYP) 3A4/5 inducers for the first 35 days of the study
7. Renal compromise (serum creatinine greater than 1.5 times the age- and sex-appropriate upper limit of normal [ULN]) at screening before the first dose of study drug
8. Severe Hepatic dysfunction (serum alanine transaminase [ALT], aspartate transaminase [AST], and/or gamma-glutamyltransferase [GGT] ALL greater than 2.5 times the age- and sex-appropriate ULN) or hepatic impairment (detectable ascites, serum bilirubin greater than 2 mg/dL, serum albumin less than 3.5 g/dL, and prothrombin time prolonged by more than 6 seconds above the ULN for the local laboratory in the absence of anticoagulant therapy) at screening before the first dose of study drug

9. Concomitant spinal cord injury or abnormality as determined by routine imaging:

   1. Conclusive radiological evidence of complete spinal cord transection
   2. Multiple injuries to the neurological spinal cord at different levels
10. History of symptomatic cervical spinal stenosis with myelopathy as a factor confounding participant assessment
11. Unlikely to be available for follow-up as specified in the protocol
12. Participated in a previous clinical study and received an investigational product within 30 days of screening
13. Previous exposure to SUN13837
14. Allergy to SUN13837 or any of its excipients
15. Any other issue which, in the opinion of the investigator, made the participant unsuitable for study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo, volume equivalent to injection 1 x daily for 28 doses
Active Comparator: SUN13837	Drug: SUN13837 injection; SUN13837 injection, injection 1 x daily for 28 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Spinal Cord Independence Measure, Version III (SCIM III) Score Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury	The SCIM III is a comprehensive rating scale that measures the ability of participants with spinal cord injury to perform everyday tasks. The SCIM III has 19 items that assess 3 domains: Self-Care (6 items, scores range from 0 to 20), Respiration and Sphincter Management (4 items, scores range from 0 to 40), and Mobility (9 items, scores range from 0 to 40). The total SCIM score ranges from 0 to a maximum of 100 points in an individual with a fully functional spinal cord. A score of 0 indicates a worse outcome and a score of 100 indicates a better outcome. An improvement of at least 4 points of the total SCIM showed a small significant improvement, and 10 points showed a substantial improvement.	Week 2, week 4, week 8 and week 16 post dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity Analyses of Total Spinal Cord Independence Measure, Version III (SCIM III) Score at Week 16 by Treatment Group	The SCIM III is a comprehensive rating scale that measures the ability of participants with spinal cord injury to perform everyday tasks. The SCIM III has 19 items that assess 3 domains: Self-Care (6 items, scores range from 0 to 20), Respiration and Sphincter Management (4 items, scores range from 0 to 40), and Mobility (9 items, scores range from 0 to 40). The total SCIM score ranges from 0 to a maximum of 100 points in an individual with a fully functional spinal cord. A score of 0 indicates a worse outcome and a score of 100 indicates a better outcome. An improvement of at least 4 points of the total SCIM showed a small significant improvement, and 10 points showed a substantial improvement.	Week 16 post dose
Change From Baseline of Total Motor Score (TMS) of International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury	TMS was the sum of the overall Upper Extremity Motor Score (UEMS) and the overall Lower Extremity Motor Score (LEMS) of ISNCSCI. The score on the scale runs from a minimum value of 0 to a maximum of 100 points in an individual with a fully functional spinal cord. A score of 0 indicates a worse outcome and a score of 100 indicates a better outcome. The UEMS was defined as the sum of the motor function scores in the cervical spinal segments C5, C6, C7, C8, and T1. A separate sum was obtained for the right and left sides (a maximum of 25 points each) and for an overall score (with a maximum score of 50). The LEMS was defined as the sum of the motor function scores in the spinal segments lumbar level 2, lumbar level 3, lumbar level 4, lumbar level 5, and sacral level 1. A separate sum was obtained for the right and left sides (a maximum of 25 points each) and for an overall score (with a maximum score of 50).	Baseline to Day 3, Week 2, Week 4, Week 8, and Week 16 post dose.
Self-Care and Mobility Subscale Scores of Spinal Cord Independence Measure, Version III (SCIM III) Score Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury	The SCIM III is a comprehensive rating scale that measures the ability of participants with spinal cord injury to perform everyday tasks. The SCIM III has 19 items that assess 3 domains, two of which are Self-care and Mobility. The self-care domain is a subscale of 6 items and scores range from 0 to 20 (higher scores indicate a better outcome). The mobility domain consists of 9 items with subscale scores range from 0 to 40 (higher scores indicate a better outcome). The score for the combined Self-Care and Mobility subscale ranges from 0 - 60 points; higher scores indicate a better outcome	Week 2, Week 4, Week 8, and Week 16 post dose.
Upper Extremity Motor Scores (UEMS) of International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord	The UEMS was defined as the sum of the motor function scores in the cervical spinal segments C5, C6, C7, C8, and T1. A separate sum was obtained for the right and left sides (a maximum of 25 points each) and an overall score of 0-50 with a maximum score of 50. A higher score indicates a better outcome.	Baseline to Day 3, Week 2, Week 4, Week 8, and Week 16 post dose.
Lower Extremity Motor Scores (LEMS) of International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury	The LEMS was defined as the sum of the motor function scores in the spinal segments lumbar level 2, lumbar level 3, lumbar level 4, lumbar level 5, and sacral level 1. A separate sum was obtained for the right and left sides (a maximum of 25 points each) and for an overall score with a maximum score of 50. A higher score indicates a better outcome.	Baseline to Day 3, Week 2, Week 4, Week 8, and Week 16 post dose.
Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury	The protocol defined an adverse event (AE) as any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.	Baseline up to approximately Day 182 post dose.

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2012
• Primary Completion (Actual): September 21, 2014
• Study Completion (Actual): September 21, 2014

Study Registration Dates

• First Submitted: December 27, 2011
• First Submitted That Met QC Criteria: December 29, 2011
• First Posted (Estimate): January 2, 2012

Study Record Updates

• Last Update Posted (Actual): January 15, 2021
• Last Update Submitted That Met QC Criteria: January 13, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: ASCI; SUN13837; Acute traumatic cervical spinal cord injury
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Wounds and Injuries; Spinal Cord Injuries
• Other Study ID Numbers: ASBI 603

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)