AC105 in Patients With Acute Traumatic Spinal Cord Injury

Study Overview
=================
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).

Official Title
-----------------
A Phase 2 Double-blind, Randomized, Placebo-controlled Study to Determine the Safety, Tolerability and Potential Activity of AC105 Following a Regimen of 6 Doses Over 30 Hours in Patients With Acute Traumatic Spinal Cord Injury (SCI).

Conditions
-----------------
Acute Spinal Cord Injury

Intervention / Treatment
-----------------
* Drug: AC105
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Saline<br>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. | Other: Placebo<br> <br> |
| Active Comparator: AC105<br>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. | Drug: AC105<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | baseline, prior to and up to 5 hours following last infusion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SCI, Acute, Traumatic, Spinal Cord Injury