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

Phase 2

Completed

• Conditions: Acute Spinal Cord Injury
• Interventions: Drug: SUN13837 injection; Drug: Placebo

• Registration Number: NCT01502631
• Lead Sponsor: Daiichi Sankyo

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-12-27
• Study First Submitted QC: 2011-12-29
• Study First Posted: 2012-01-02
• Study Start: 2012-08-08
• Primary Completion: 2014-09-21
• Study Completion: 2014-09-21
• Disposition First Submitted: 2016-08-23
• Disposition First Submitted QC: 2016-08-23
• Disposition First Posted: 2016-08-25
• Results First Submitted: 2020-12-10
• Status Verified: 2021-01
• Results First Submitted QC: 2021-01-13
• Last Update Submitted: 2021-01-13
• Results First Posted: 2021-01-15
• Last Update Posted: 2021-01-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 65

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SUN13837	SUN13837 injection	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Total Spinal Cord Independence Measure, Version III (SCIM III) Score Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury	Week 2, week 4, week 8 and week 16 post dose.	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.

Secondary Outcome Measures

Name	Time	Method
Sensitivity Analyses of Total Spinal Cord Independence Measure, Version III (SCIM III) Score at Week 16 by Treatment Group	Week 16 post dose	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.
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	Baseline to Day 3, Week 2, Week 4, Week 8, and Week 16 post dose.	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).
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	Week 2, Week 4, Week 8, and Week 16 post dose.	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
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	Baseline to Day 3, Week 2, Week 4, Week 8, and Week 16 post dose.	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.
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	Baseline to Day 3, Week 2, Week 4, Week 8, and Week 16 post dose.	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.
Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury	Baseline up to approximately Day 182 post dose.	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.