Acute Spinal Cord Injury
Conditions
Keywords
Acute, Traumatic, SCI, Spinal Cord Injury
Brief summary
The principal aim of this study was to establish the feasibility of rapid administration, safety, and tolerability of AC105 in patients with acute spinal cord injury.
Detailed description
To determine safety and tolerability of AC105 following a regimen of 6 intravenous doses over 30 hours in patients with acute non-penetrating traumatic spinal cord injury (SCI).
Interventions
DRUGAC105
OTHERPlacebo
Sponsors
United States Department of Defense
DP Clinical, Inc.
Acorda Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female between 18 and 65 years of age, inclusive * Acute traumatic SCI, at a neurological level between C4 and T11 * No evidence of penetrating or transection injury (e.g. caused by projectile or stab wound) * Neurological ASIA Impairment Scale A, B or C * Patient is able to provide written or verbal witnessed consent. If unable to provide either, consent may be provided by legally authorized representative (LAR) * Patient is able to initiate treatment within time window of injury
Exclusion criteria
* Known allergy or hypersensitivity to polyethylene glycol * Mental impairment or other conditions that would preclude a reliable ASIA exam or adequate consent * Positive urine pregnancy test result * Serum creatinine level ≥ 2 mg/dL * History or active renal failure or dialysis * Mean arterial blood pressure \< 60 mmHg despite vasopressor treatment * On a current regimen of digoxin * Chronic use of magnesium salts prior to the SCI (within 1week of presentation) and/or the use of magnesium salts in the acute care setting prior to the administration of investigational product * Any other medical condition that, in the judgment of the investigator, would preclude provision of informed consent, make participation in the study unsafe, or unreasonably complicate follow-up or the interpretation of study outcome data or may otherwise interfere with achieving the study objectives * In the judgment of the Investigator, cannot adequately provide informed consent, is likely to be non-compliant, or may be unable to cooperate with study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | up to 6 months | Treatment-Emergent Adverse Events (TEAEs) are defined as AEs with date time of onset (or worsening) on or after the start date time of the first infusion and no more than 30 days after the end of the last infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameters of AC105 Using Individual Patient Plasma Concentration-time Data | baseline, prior to and up to 5 hours following last infusion | Measuring Maximum Measured Plasma Concentration (Cmax), Time to Maximum Measured Plasma Concentration (Tmax), Half-life calculated as In(2)/kel (T 1/2) and Area Under the Plasma Concentration versus time curve (AUC). |
Participant flow
Recruitment details
A total of 15 subjects were enrolled. 2 subjects randomized to placebo were subsequently deemed ineligible and were not treated with the investigational product; they were excluded from the analysis. A total of 13 subjects received at least 1 infusion of the investigational product (AC105 and placebo) and were included in the Safety Population.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients randomized (1:1) to the placebo arm will receive an initial intravenous infusion of saline for 30 minutes within a pre-specified time window (12, 9, 6 hours post-injury). Patients will receive 5 additional infusions of the same dose and duration at 6 -hour intervals.
Placebo | 6 |
| AC105 Patients randomized (1:1) to the active drug arm will receive an initial intravenous infusion of AC105 for 30 minutes within a pre-specified time window (12, 9, 6 hours post-injury). Patients will receive 5 additional infusions of the same dose and duration at 6 -hour intervals.
AC105 | 7 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Non-compliance with Study Drug | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawn by Sponsor | 0 | 1 |
Baseline characteristics
| Characteristic | AC105 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 38.3 years STANDARD_DEVIATION 6.23 | 37.7 years STANDARD_DEVIATION 4.5 | 37.0 years STANDARD_DEVIATION 7.12 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 11 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 6 | 0 / 7 |
| other Total, other adverse events | 4 / 6 | 6 / 7 |
| serious Total, serious adverse events | 1 / 6 | 2 / 7 |
Outcome results
Primary
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Treatment-Emergent Adverse Events (TEAEs) are defined as AEs with date time of onset (or worsening) on or after the start date time of the first infusion and no more than 30 days after the end of the last infusion.
Time frame: up to 6 months
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Mild TEAEs | 4 participants |
| Placebo | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Moderate TEAEs | 3 participants |
| Placebo | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Severe TEAEs | 2 participants |
| Placebo | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Serious TEAEs | 1 participants |
| Placebo | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Drug-related TEAEs | 0 participants |
| Placebo | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | TEAEs Leading to Death | 1 participants |
| AC105 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Drug-related TEAEs | 2 participants |
| AC105 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Mild TEAEs | 6 participants |
| AC105 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Serious TEAEs | 2 participants |
| AC105 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Moderate TEAEs | 5 participants |
| AC105 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | TEAEs Leading to Death | 0 participants |
| AC105 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Severe TEAEs | 3 participants |
Secondary
Pharmacokinetic (PK) Parameters of AC105 Using Individual Patient Plasma Concentration-time Data
Measuring Maximum Measured Plasma Concentration (Cmax), Time to Maximum Measured Plasma Concentration (Tmax), Half-life calculated as In(2)/kel (T 1/2) and Area Under the Plasma Concentration versus time curve (AUC).
Time frame: baseline, prior to and up to 5 hours following last infusion
Population: No subjects were analyzed. No data was collected. There was a change in the planned analysis to not perform formal PK analysis for a terminated study and abbreviated Clinical Study Report.