Acute Spinal Cord Injury
Conditions
Keywords
ASCI, SUN13837, Acute traumatic cervical spinal cord injury
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.
Interventions
DRUGSUN13837 injection
SUN13837 injection, injection 1 x daily for 28 doses
DRUGPlacebo
Matching placebo, volume equivalent to injection 1 x daily for 28 doses
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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. |
| 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. |
Countries
Canada, Czechia, France, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 65 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study at 19 clinic sites in the United States of America, 2 in France, 1 in the United Kingdom,1 in Spain, and 1 in the Czech Republic. Four (4) of the participants were not treated. The data on the 61 treated participants are presented in this report.
Pre-assignment details
Participants with acute traumatic cervical spinal cord injury (ASCI) within 12 hours of treatment were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| SUN13837 Participants with acute traumatic cervical spinal cord injury who were administered SUN13837 injection once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day \[dosing to 27 days\] in certain participants). | 30 |
| Placebo Participants with acute traumatic cervical spinal cord injury who were administered a placebo once daily for at least 7 but no more than 28 consecutive days (except for the dose interval between the first and second doses, which may have occurred on the same day \[dosing to 27 days\] in certain participants). | 31 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 8 |
| Overall Study | Investigator's decision | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Other | 10 | 5 |
| Overall Study | Participant non-compliant | 1 | 0 |
| Overall Study | Participant withdrew consent | 2 | 4 |
Baseline characteristics
| Characteristic | SUN13837 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 37.9 years STANDARD_DEVIATION 16.6 | 38.8 years STANDARD_DEVIATION 17.2 | 38.4 years STANDARD_DEVIATION 16.8 |
| Age, Customized < 55 years | 25 Participants | 25 Participants | 50 Participants |
| Age, Customized ≥ 55 years | 5 Participants | 6 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 26 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 22 Participants | 17 Participants | 39 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 26 Participants | 26 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 30 | 2 / 31 |
| other Total, other adverse events | 14 / 30 | 20 / 31 |
| serious Total, serious adverse events | 21 / 30 | 23 / 31 |
Outcome results
Primary
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.
Time frame: Week 2, week 4, week 8 and week 16 post dose.
Population: Total Spinal Cord Independence Measure was assessed in the intent-to-treat (ITT) population, defined as all randomized participants who had at least 1 SCIM III evaluation and received at least 7 (partial or complete) IV bolus dose injections of the study drug in SUN13837 group or in Placebo group.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| SUN13837 | 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 | 15.87 Score on a scale |
| SUN13837 | 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 8 | 28.77 Score on a scale |
| SUN13837 | 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 4 | 22.56 Score on a scale |
| SUN13837 | 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 16 | 38.14 Score on a scale |
| Placebo | 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 16 | 33.60 Score on a scale |
| Placebo | 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 | 10.26 Score on a scale |
| Placebo | 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 4 | 15.69 Score on a scale |
| Placebo | 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 8 | 25.74 Score on a scale |
Comparison: Difference (SUN13837 - Placebo) at Week 2p-value: 0.218290% CI: [-1.93, 13.14]Mixed Model Repeated Measures (MMRM)
Comparison: Difference (SUN13837 - Placebo) at Week 4p-value: 0.22690% CI: [-2.54, 16.27]Mixed Model Repeated Measures (MMRM)
Comparison: Difference (SUN13837 - Placebo) at Week 8p-value: 0.618490% CI: [-7.15, 13.21]Mixed Model Repeated Measures (MMRM)
Comparison: Difference (SUN13837 - Placebo) at Week 16p-value: 0.491290% CI: [-6.48, 15.56]Mixed Model Repeated Measures (MMRM)
Secondary
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).
Time frame: Baseline to Day 3, Week 2, Week 4, Week 8, and Week 16 post dose.
Population: Total Motor Score (TMS) was assessed in the intent-to-treat (ITT) population, defined as all randomized participants who had at least 1 SCIM III evaluation and received at least 7 (partial or complete) IV bolus dose injections of the study drug in SUN13837 group or in Placebo group.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| SUN13837 | 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 | Week 2 | 8.66 Units on a scale |
| SUN13837 | 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 | Week 8 | 14.81 Units on a scale |
| SUN13837 | 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 | Week 4 | 11.96 Units on a scale |
| SUN13837 | 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 | Week 16 | 16.58 Units on a scale |
| SUN13837 | 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 | Day 3 | 5.84 Units on a scale |
| Placebo | 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 | Week 16 | 14.07 Units on a scale |
| Placebo | 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 | Day 3 | 1.20 Units on a scale |
| Placebo | 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 | Week 2 | 4.04 Units on a scale |
| Placebo | 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 | Week 4 | 6.35 Units on a scale |
| Placebo | 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 | Week 8 | 11.31 Units on a scale |
Secondary
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.
Time frame: Baseline up to approximately Day 182 post dose.
Population: The safety population was used to assess adverse events.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Decubitus ulcer | 13 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Leukocytosis | 8 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Nausea | 12 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Pyrexia | 17 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Musculoskeletal pain | 10 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Muscle spasticity | 12 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Orthostatic hypotension | 9 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Insomnia | 14 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Anaemia | 5 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Neuralgia | 13 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Respiratory failure | 8 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Urinary tract infection | 21 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Muscle spasms | 8 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Anxiety | 9 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Headache | 9 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Pneumonia | 9 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Rash | 9 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Constipation | 7 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Blood creatine phosphokinase increased | 7 Participants |
| SUN13837 | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Depression | 8 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Blood creatine phosphokinase increased | 5 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Urinary tract infection | 23 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Pyrexia | 14 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Decubitus ulcer | 13 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Insomnia | 12 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Pneumonia | 17 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Nausea | 10 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Muscle spasticity | 9 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Neuralgia | 8 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Anxiety | 10 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Constipation | 11 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Leukocytosis | 10 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Depression | 9 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Musculoskeletal pain | 7 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Orthostatic hypotension | 8 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Anaemia | 11 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Respiratory failure | 7 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Muscle spasms | 6 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Headache | 4 Participants |
| Placebo | Incidence of Adverse Events Reported in ≥ 20% of Participants Following Treatment With SUN13837 Injection or Placebo in Adult With Acute Spinal Cord Injury | Rash | 4 Participants |
Secondary
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.
Time frame: Baseline to Day 3, Week 2, Week 4, Week 8, and Week 16 post dose.
Population: Lower Extremity Motor Scores (LEMS) were assessed in the intent-to-treat (ITT) population, defined as all randomized participants who had at least 1 SCIM III evaluation and received at least 7 (partial or complete) IV bolus dose injections of the study drug in SUN13837 group or in Placebo group.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| SUN13837 | 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 | Week 4 | 4.89 Units on a scale |
| SUN13837 | 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 | Day 3 | 2.71 Units on a scale |
| SUN13837 | 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 | Week 8 | 5.08 Units on a scale |
| SUN13837 | 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 | Week 16 | 6.13 Units on a scale |
| SUN13837 | 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 | Week 2 | 3.66 Units on a scale |
| Placebo | 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 | Week 16 | 9.96 Units on a scale |
| Placebo | 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 | Day 3 | 3.22 Units on a scale |
| Placebo | 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 | Week 4 | 5.36 Units on a scale |
| Placebo | 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 | Week 8 | 8.30 Units on a scale |
| Placebo | 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 | Week 2 | 4.28 Units on a scale |
Secondary
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
Time frame: Week 2, Week 4, Week 8, and Week 16 post dose.
Population: Self-Care and Mobility Subscale Scores were assessed in the intent-to-treat (ITT) population, defined as all randomized participants who had at least 1 SCIM III evaluation and received at least 7 (partial or complete) IV bolus dose injections of the study drug in SUN13837 group or in Placebo group.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| SUN13837 | 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 16 | 18.73 Score on a scale |
| SUN13837 | 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 8 | 14.70 Score on a scale |
| SUN13837 | 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 4 | 9.18 Score on a scale |
| SUN13837 | 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 | 5.76 Score on a scale |
| Placebo | 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 16 | 15.02 Score on a scale |
| Placebo | 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 | 3.77 Score on a scale |
| Placebo | 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 4 | 6.45 Score on a scale |
| Placebo | 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 8 | 11.25 Score on a scale |
Secondary
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.
Time frame: Week 16 post dose
Population: Sensitivity analyses were assessed in the Intent-to-Treat (ITT) and Efficacy Evaluable (EE) populations. The EE Population consisted of all subjects in the ITT Population who did not have any major protocol violations that impacted efficacy and were observed for efficacy for at least 2 SCIM III evaluations.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| SUN13837 | Sensitivity Analyses of Total Spinal Cord Independence Measure, Version III (SCIM III) Score at Week 16 by Treatment Group | Primary (EE) | 38.25 Score on a scale |
| SUN13837 | Sensitivity Analyses of Total Spinal Cord Independence Measure, Version III (SCIM III) Score at Week 16 by Treatment Group | Multiple Imputation (ITT) | 37.96 Score on a scale |
| SUN13837 | Sensitivity Analyses of Total Spinal Cord Independence Measure, Version III (SCIM III) Score at Week 16 by Treatment Group | LOCF (ITT) | 36.12 Score on a scale |
| SUN13837 | Sensitivity Analyses of Total Spinal Cord Independence Measure, Version III (SCIM III) Score at Week 16 by Treatment Group | Simple Multiple Imputation (ITT) | 38.49 Score on a scale |
| Placebo | Sensitivity Analyses of Total Spinal Cord Independence Measure, Version III (SCIM III) Score at Week 16 by Treatment Group | LOCF (ITT) | 30.84 Score on a scale |
| Placebo | Sensitivity Analyses of Total Spinal Cord Independence Measure, Version III (SCIM III) Score at Week 16 by Treatment Group | Primary (EE) | 30.48 Score on a scale |
| Placebo | Sensitivity Analyses of Total Spinal Cord Independence Measure, Version III (SCIM III) Score at Week 16 by Treatment Group | Simple Multiple Imputation (ITT) | 32.00 Score on a scale |
| Placebo | Sensitivity Analyses of Total Spinal Cord Independence Measure, Version III (SCIM III) Score at Week 16 by Treatment Group | Multiple Imputation (ITT) | 32.17 Score on a scale |
Secondary
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.
Time frame: Baseline to Day 3, Week 2, Week 4, Week 8, and Week 16 post dose.
Population: Upper Extremity Motor Scores (UEMS) were assessed in the intent-to-treat (ITT) population, defined as all randomized participants who had at least 1 SCIM III evaluation and received at least 7 (partial or complete) IV bolus dose injections of the study drug in SUN13837 group or in Placebo group.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| SUN13837 | 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 | Week 8 | 8.66 Units on a scale |
| SUN13837 | 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 | Day 3 | 2.08 Units on a scale |
| SUN13837 | 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 | Week 2 | 3.98 Units on a scale |
| SUN13837 | 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 | Week 4 | 5.95 Units on a scale |
| SUN13837 | 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 | Week 16 | 9.92 Units on a scale |
| Placebo | 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 | Week 16 | 4.95 Units on a scale |
| Placebo | 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 | Week 4 | 1.73 Units on a scale |
| Placebo | 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 | Day 3 | -1.24 Units on a scale |
| Placebo | 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 | Week 8 | 3.83 Units on a scale |
| Placebo | 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 | Week 2 | 0.59 Units on a scale |