AC105 in Patients With Acute Traumatic Spinal Cord Injury

• Sponsor: Acorda Therapeutics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01750684
• Collaborator: United States Department of Defense (U.S. Fed), DP Clinical, Inc. (Industry)
• Enrollment: 15
• Arms: 2
• Duration (Months): 22

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Spinal Cord Injury	Drug: AC105; Other: Placebo	Phase 2

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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).
• Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Saline 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
Active Comparator: 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.	Drug: AC105

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Acorda Therapeutics
• United States Department of Defense
• DP Clinical, Inc.

Investigators

• Study Director: Andrew Eisen, MD, Acorda Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Acorda Therapeutics
• ClinicalTrials.gov Identifier: NCT01750684
• Other Study ID Numbers: ACPM-SI-1009
• First Posted: Dec 17, 2012
• Last Update Posted: Nov 6, 2018
• Last Verified: Oct 1, 2018

• Keywords provided by Acorda Therapeutics: Acute; Traumatic; SCI; Spinal Cord Injury
• Additional relevant MeSH terms: Spinal Cord Injuries; Wounds and Injuries

Study Results

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.

Arm/Group Title	Placebo	AC105
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	6	7
COMPLETED	4	5
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Placebo	AC105	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	6	7	13
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.0 (7.12)	38.3 (6.23)	37.7 (4.50)
Sex: Female, Male (Count of Participants)
Female	1 16.7%	1 14.3%	2 15.4%
Male	5 83.3%	6 85.7%	11 84.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 16.7%	0 0%	1 7.7%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	2 28.6%	2 15.4%
White	5 83.3%	5 71.4%	10 76.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Placebo	AC105
Arm/Group Description	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	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
Measure Participants	6	7
Mild TEAEs	4 66.7%	6 85.7%
Moderate TEAEs	3 50%	5 71.4%
Severe TEAEs	2 33.3%	3 42.9%
Serious TEAEs	1 16.7%	2 28.6%
Drug-related TEAEs	0 0%	2 28.6%
TEAEs Leading to Death	1 16.7%	0 0%

2. Secondary Outcome

Title	Pharmacokinetic (PK) Parameters of AC105 Using Individual Patient Plasma Concentration-time Data
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Saline	AC105
Arm/Group Description	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	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
Measure Participants	0	0

Adverse Events

Time Frame	Up to 6 months.
Adverse Event Reporting Description	TEAEs are defined as adverse events (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. Adverse events were classified according to Version 16.0 of the Medical Dictionary for Regulatory Activities (MedDRA) coding dictionary.
Arm/Group Title	Placebo		AC105
Arm/Group Description	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		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
All Cause Mortality
	Placebo		AC105
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		0/7 (0%)
Serious Adverse Events
	Placebo		AC105
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		2/7 (28.6%)
Infections and infestations
Pneumonia	0/6 (0%)		2/7 (28.6%)
Injury, poisoning and procedural complications
Wound dehiscence	1/6 (16.7%)		0/7 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/6 (0%)		1/7 (14.3%)
Respiratory arrest	1/6 (16.7%)		0/7 (0%)
Respiratory failure	1/6 (16.7%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		AC105
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)		6/7 (85.7%)
Gastrointestinal disorders
Nausea	2/6 (33.3%)		4/7 (57.1%)
Ileus	0/6 (0%)		2/7 (28.6%)
Constipation	1/6 (16.7%)		1/7 (14.3%)
Neurogenic bowel	1/6 (16.7%)		1/7 (14.3%)
General disorders
Pyrexia	1/6 (16.7%)		1/7 (14.3%)
Infections and infestations
Pneumonia	2/6 (33.3%)		3/7 (42.9%)
Urinary tract infection	1/6 (16.7%)		2/7 (28.6%)
Investigations
Oxygen saturation decreased	0/6 (0%)		2/7 (28.6%)
Musculoskeletal and connective tissue disorders
Muscle spasms	2/6 (33.3%)		0/7 (0%)
Nervous system disorders
Neuralgia	2/6 (33.3%)		2/7 (28.6%)
Psychiatric disorders
Anxiety	2/6 (33.3%)		3/7 (42.9%)
Depression	3/6 (50%)		2/7 (28.6%)
Insomnia	0/6 (0%)		2/7 (28.6%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/6 (0%)		2/7 (28.6%)
Respiratory failure	2/6 (33.3%)		0/7 (0%)
Skin and subcutaneous tissue disorders
Rash	1/6 (16.7%)		1/7 (14.3%)
Vascular disorders
Hypotension	2/6 (33.3%)		2/7 (28.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor (Acorda) has right to review and comment on proposed publications within a specified time frame, up to 60 days; multi-center trials require joint publication unless specifically permitted otherwise.