• Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 Post-dose to 28-days after last dose ]
  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.
• Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 [ Time Frame: Day 1 pre-dose up to Day 29 ]
  AXER-204 will be measured in cerebrospinal fluid (CSF) and in serum

• Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 Post-dose to 28-days after last dose ]
  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.
• Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 [ Time Frame: Day 1 pre-dose up to Day 29 ]
  AXER-204 will be measured in cerebrospinal fluid (CSF) and in serum
• Change in International Standards for Neurological Classification of SCI (ISNCSCI) Upper Extremity Motor Score (UEMS) [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
  The ISNCSCI scale includes a Motor and Sensory examination for each side of the body (left/right). The Sensory examination involves 'light touch' and 'pinprick' for each dermatome (28) on both sides of the body (total 56). A score of 0, 1 or 2 can be given to each dermatome resulting in a total max. of 112 points. The Motor level is determined by examining the muscle function within each of the 10 myotomes on each side of the body (20 myotomes in total). A score ranging from 1 to 5 can be given to each myotome tested resulting in a maximum score of 100 (50 for upper extremity and 50 for lower extremity). Higher values indicate better function with the maximum scores corresponding to normal function.

• Change in International Standards for Neurological Classification of SCI (ISNCSCI) Upper Extremity Motor Score (UEMS) [ Time Frame: Baseline to Day 169 and Day 253 ]
  The ISNCSCI scale includes a Motor and Sensory examination for each side of the body (left/right). The Sensory examination involves 'light touch' and 'pinprick' for each dermatome (28) on both sides of the body (total 56). A score of 0, 1 or 2 can be given to each dermatome resulting in a total max. of 112 points. The Motor level is determined by examining the muscle function within each of the 10 myotomes on each side of the body (20 myotomes in total). A score ranging from 1 to 5 can be given to each myotome tested resulting in a maximum score of 100 (50 for upper extremity and 50 for lower extremity). Higher values indicate better function with the maximum scores corresponding to normal function.
• Change in Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) scores [ Time Frame: Baseline to Day 169 and Day 253 ]
  The GRASSP is a clinical impairment measure for the upper limb for use after tetraplegia. The measure includes domains which are important in describing hand function: Strength with scores from 0-50 for each side, Sensory testing with scores ranging from 0-12 for each hand, Prehension ability with scores 0-12 for each hand, and Prehension performance with scores from 0-30 for each hand. Higher subscores indicate better function.
• Change in version III of the Spinal Cord Independence Measure (SCIM III) self-care and mobility domain scores [ Time Frame: Baseline to Day 169 and Day 253 ]
  The SCIM III is a questionnaire that assesses activities of daily living (ADL) regarding self-care, mobility, respiration, and sphincter management. The self-care and mobility domains have scores ranging from 0-20 and 0-40 respectively. Higher scores correspond to better ability to carry out ADL.

• Change in International Standards for Neurological Classification of SCI (ISNCSCI) motor and sensory scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
  The ISNCSCI scale includes a Motor and Sensory examination for each side of the body (left/right). The Sensory examination involves 'light touch' and 'pinprick' for each dermatome (28) on both sides of the body (total 56). A score of 0, 1 or 2 can be given to each dermatome resulting in a total max. of 112 points. The Motor level is determined by examining the muscle function within each of the 10 myotomes on each side of the body (20 myotomes in total). A score ranging from 1 to 5 can be given to each myotome tested resulting in a maximum score of 100 (50 for upper extremity and 50 for lower extremity). Higher values indicate better function with the maximum scores corresponding to normal function.
• Change in Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
  The GRASSP is a clinical impairment measure for the upper limb for use after tetraplegia. The measure includes domains which are important in describing hand function: Strength with scores from 0-50 for each side, Sensory testing with scores ranging from 0-12 for each hand, Prehension ability with scores 0-12 for each hand, and Prehension performance with scores from 0-30 for each hand. Higher subscores indicate better function.
• Change in version III of the Spinal Cord Independence Measure (SCIM III) self-care and mobility domain scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
  The SCIM III is a questionnaire that assesses activities of daily living (ADL) regarding self-care, mobility, respiration, and sphincter management. The self-care and mobility domains have scores ranging from 0-20 and 0-40 respectively. Higher scores correspond to better ability to carry out ADL.
• Change in Capabilities of Upper Extremity Test (CUE-T) scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
  The CUE-T is a clinical impairment measure for upper limb use after tetraplegia. The test has 19 items (17 unilateral and tested separately for the right and left upper extremities; two bilateral items) that are scored on a five-point scale (0-4) using one of three scoring dimensions (number of times task is completed; amount of weight; amount of time). The total assessment has a possible range in scores from 0 to 144. Higher scores correspond to better function.
• Change in Capabilities of Upper Extremity Questionnaire (CUE-Q) scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
  The CUE-Q is a questionnaire to assess arm and hand function comprised of 17 questions with scores of 0-4 assigned to each side for each question resulting in a total score ranging from 0-136. A higher score corresponds to better function.
• Change in SF - 36 v2 Health Survey scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
  The Short Form-36 is a 36-question, 8-domain survey designed to assess physical and emotional health. Raw scores can be converted to normalized values ranging from 0-100 for each domain. Each domain has a normal score of 50 with lower scores indicating progressively poorer health.
• Change in Neuro-QOL Item Bank v1.0 - Upper Extremity Function questionnaire scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
  The Neuro-Quality of Life Item Bank v1.0 - Upper Extremity Function questionnaire consists of 20 questions focused on activities of activities of daily living (ADL) requiring use of arms and hands. Scores for each question range from 1-5 resulting in a total maximum score of 100. A higher score corresponds to greater ability to conduct ADL.

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.

• Drug: AXER-204
  human NoGo Trap fusion protein
  Other Names:

  • human NoGo Trap
  • human Nogo Receptor decoy
• Drug: Placebo
  Phosphate buffered saline formulation

• Experimental: AXER-204
  Part 1 - Single ascending doses; Part 2 - Repeated dose
  Intervention: Drug: AXER-204
• Placebo Comparator: Placebo
  Part 2 only - Repeated dose
  Intervention: Drug: Placebo

Key Inclusion Criteria:

1. Traumatic spinal cord injury that occurred ≥ 1 year ago
2. 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

3. Confirmation by MRI of the following:

   1. Chronic SCI (persistent spinal cord lesion)
   2. 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
   3. CSF space spanning the lesion

Key Exclusion Criteria:

1. Penetrating injury to the cord or spinal cord trauma caused by ballistic injury including gunshot that did not penetrate the spinal cord
2. History of stroke, cerebrovascular injury, or elevated intracranial pressure
3. Contraindications for lumbar puncture
4. Requiring mechanical ventilatory assistance of any type
5. Body mass index (BMI) ≥ 35 kg/m2 or body weight <50 kg
6. 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
7. Subjects fitted with an implanted pump or port for delivery of therapeutics to the CSF
8. Uncontrolled medical condition including but not limited to cardiovascular disease, sleep apnea, obstructive lung disease, severe neuropathic or severe chronic pain, severe autonomic dysreflexia
9. 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.