Title
AXER-204 in Participants With Chronic Spinal Cord Injury
A Multicenter, Two Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AXER-204 in Subjects With Chronic Spinal Cord Injury
Phase
Phase 1/Phase 2Lead Sponsor
ReNetX BioStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Chronic Spinal Cord InjuryIntervention/Treatment
AXER-204 ...Study Participants
52This 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.
human NoGo Trap fusion protein
Phosphate buffered saline formulation
Key Inclusion Criteria: Traumatic spinal cord injury that occurred ≥ 1 year ago Cervical spinal cord injury with serious neurologic deficit as evidenced by 1) bilateral ISNCSCI UEMS between 4 and 36 points inclusive, and 2) bilateral GRASSP Prehension Ability score between 4 and 17 points inclusive Confirmation by MRI of the following: Chronic SCI (persistent spinal cord lesion) For AIS grade of A without sensory or motor zone of partial preservation extending at least two levels caudal to the level of injury, no apparent transection of the cord CSF space spanning the lesion Key Exclusion Criteria: Penetrating injury to the cord or spinal cord trauma caused by ballistic injury including gunshot that did not penetrate the spinal cord History of stroke, cerebrovascular injury, or elevated intracranial pressure Contraindications for lumbar puncture Requiring mechanical ventilatory assistance of any type Body mass index (BMI) ≥ 35 kg/m2 or body weight <50 kg History of life threatening allergic or immune-mediated reaction to vaccines, or biologic drugs, at any time or any life threatening allergic or immune-mediated reaction within the past 12 months Subjects fitted with an implanted pump or port for delivery of therapeutics to the CSF Uncontrolled medical condition including but not limited to cardiovascular disease, sleep apnea, obstructive lung disease, severe neuropathic or severe chronic pain, severe autonomic dysreflexia Participation in any other investigational drug or device trial within 30 days or within 5 half-lives of the investigational drug or any past participation in a SCI cellular therapy trial. Note: Other protocol defined Inclusion/Exclusion criteria may apply.
| Event Type | Organ System | Event Term | Part 1 - AXER-204 - 3 mg | Part 1 - AXER-204 - 30 mg | Part 1 - AXER-204 - 90 mg | Part 1 - AXER-204 - 200 mg | Part 2 - AXER-204 - 200 mg | Part 2 - Placebo |
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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.
Volume of distribution calculated from serum exposure data
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.
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.
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.
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.
