This two-part trial will assess the safety, tolerability, pharmacokinetics, and efficacy of AXER-204 administered by lumbar puncture and slow bolus infusion. Part 1 will evaluate the safety, tolerability, and pharmacokinetics of single ascending doses of AXER-204. Part 2 will evaluate the safety, tolerability, pharmacokinetics, and efficacy of repeated doses AXER-204 in comparison to placebo.
AXER-204 is a human fusion protein that acts as a soluble decoy/trap for the myelin-associated inhibitors of axonal growth known as Nogo-A, MAG, and OMgp. AXER-204 and a surrogate protein used in early preclinical studies have been found to promote axon growth and recovery of function in animal models of spinal cord injury. Part 1 of the trial is a multicenter, open-label, single ascending dose study in participants with chronic cervical spinal cord injury. Four cohorts of 6 participants each are planned, with participants within each cohort expected to receive the same dose of AXER-204. Part 2 is a multicenter, randomized, double-blind, placebo-controlled, repeat dose study in chronic cervical spinal cord injury participants. Approximately 32 participants will be randomized (ratio 1:1) to receive repeated doses of AXER-204 or placebo (a phosphate buffered saline formulation). The dose level and dose frequency will be dependent upon outcomes from Part 1.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
52
Keck Medicine of USC
Los Angeles, California, United States
Shepherd Center
Atlanta, Georgia, United States
Shirley Ryan AbilityLab / Northwestern
Chicago, Illinois, United States
Spaulding Rehabilitation
Boston, Massachusetts, United States
Incidence of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, or is a medically important event.
Time frame: Up to Day 29 for Part 1 and Day 253 for Part 2
Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in Serum
Time frame: Part 1: pre-dose and 1 h, 6 h, 12 h, and 24 h post-dose, Day 4, 8, 15, and 29, Part 2: pre-dose and 4 h post-dose on days 1, 21, 42, 63, and 104; and on Study Days 169 and 253.
Cmax in Serum
Time frame: Part 1: pre-dose and 1 h, 6 h, 12 h, and 24 h post-dose, Day 4, 8, 15, and 29, Part 2: pre-dose and 4 h post-dose on days 1, 21, 42, 63, and 104; and on Study Days 169 and 253.
Tmax in Serum
Time frame: Part 1: pre-dose and 1 h, 6 h, 12 h, and 24 h post-dose, Day 4, 8, 15, and 29, Part 2: pre-dose and 4 h post-dose on days 1, 21, 42, 63, and 104; and on Study Days 169 and 253.
t1/2 in Serum
Time frame: Part 1: pre-dose and 1 h, 6 h, 12 h, and 24 h post-dose, Day 4, 8, 15, and 29, Part 2: pre-dose and 4 h post-dose on days 1, 21, 42, 63, and 104; and on Study Days 169 and 253.
Clearance From Serum
Time frame: Day 1 pre-dose up to Day 29 in Part 1, Pre-dose up to Day 253 in Part 2
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The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Volume of Distribution
Volume of distribution calculated from serum exposure data
Time frame: Part 1: pre-dose and 1 h, 6 h, 12 h, and 24 h post-dose, Day 4, 8, 15, and 29, Part 2: pre-dose and 4 h post-dose on days 1, 21, 42, 63, and 104; and on Study Days 169 and 253.
Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in CSF
Time frame: Part 1: pre-dose, post-dose at 24 h, 72 h, Days 8 and 29, Part 2: pre-dose on Days 1, 21, 42, 63, and 104, and on Day 253.
Cmax of AXER-204 in CSF
Time frame: Part 1: pre-dose, post-dose at 24 h, 72 h, Days 8 and 29, Part 2: pre-dose on Days 1, 21, 42, 63, and 104, and on Day 253.
Tmax of AXER-204 in CSF
Time frame: Part 1: pre-dose, post-dose at 24 h, 72 h, Days 8 and 29, Part 2: pre-dose on Days 1, 21, 42, 63, and 104, and on Day 253.
t1/2 of AXER-204 in CSF
Time frame: Part 1: pre-dose, post-dose at 24 h, 72 h, Days 8 and 29, Part 2: pre-dose on Days 1, 21, 42, 63, and 104, and on Day 253.
Change in International Standards for Neurological Classification of SCI (ISNCSCI) Bilateral Upper Extremity Motor Score (UEMS)
The ISNCSCI bilateral Upper Extremity Motor Score (UEMS) is determined by examining the muscle function within each of the 5 myotomes encompassing arm and hand function on each side of the body. A score ranging from 0 to 5 can be given to each myotome tested resulting in a maximum score of 50. Higher values indicate greater strength.
Time frame: Baseline to Day 169
Change in Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) Bilateral Prehension Performance Score
The GRASSP Bilateral Prehension Performance Score is determined based on performance of four tasks with each hand with scores ranging from 0 to 5 for each task resulting in a maximum score of 40. Higher scores indicate better function.
Time frame: Baseline to Day 169
Change in Version III of the Spinal Cord Independence Measure (SCIM III) Self-care
The SCIM III questionnaire self-care score assesses activities of daily living including feeding, bathing, dressing, and grooming. The self-care score ranges 0-20 with higher scores correspond to better ability to carry out these self-care activities.
Time frame: Baseline to Day 169
Patient Global Impression of Change (PGIC) Responder Rate
The PGIC instrument captures the patient's overall evaluation of response to treatment. Specifically, the PGIC asks: "Since beginning this clinical trial, how would you describe the overall change (if any) related to your chronic spinal cord injury?" The patient is asked to report the degree to which they have changed since entering the treatment period using a 7-point Likert scale (1='Much worse', 2='Worse', 3='A little worse', 4='No change', 5='A little better', 6='Better', 7='Much better') and "If better or worse, what has changed?". Patients that have evaluation results including "Much better", "Better", or "A little better" are considered Responders.
Time frame: Day 169