Chronic Spinal Cord Injury
Conditions
Keywords
myelin-associated inhibitor, Nogo-A, MAG, OMgp, Nogo Receptor
Brief summary
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.
Detailed description
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.
Interventions
DRUGAXER-204
human NoGo Trap fusion protein
DRUGPlacebo
Phosphate buffered saline formulation
Sponsors
ReNetX Bio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Part 1 - None; Part 2 - Quadruple
Intervention model description
Part 1 is open-label single-ascending dose. Part 2 is double-blind, placebo-controlled, repeat dose.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| t1/2 of AXER-204 in CSF | 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. | — |
| Volume of Distribution | 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. | Volume of distribution calculated from serum exposure data |
| Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in CSF | 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 | 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 | 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. | — |
| Incidence of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Day 29 for Part 1 and Day 253 for Part 2 | 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 in Serum | 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 | 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 | 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 | 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 | Day 1 pre-dose up to Day 29 in Part 1, Pre-dose up to Day 253 in Part 2 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) Bilateral Prehension Performance Score | Baseline to Day 169 | 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. |
| Change in Version III of the Spinal Cord Independence Measure (SCIM III) Self-care | Baseline to Day 169 | 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. |
| Patient Global Impression of Change (PGIC) Responder Rate | Day 169 | 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. |
| Change in International Standards for Neurological Classification of SCI (ISNCSCI) Bilateral Upper Extremity Motor Score (UEMS) | Baseline to Day 169 | 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. |
Countries
United States
Participant flow
Recruitment details
Part 1: 25 participants were enrolled. One patient was withdrawn from the study prior to dosing and is not included in the Safety Population used for data analyses. Part 2: 27 participants were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 - AXER-204 - 3 mg Part 1 Open-label single ascending dose. Participants received a single dose of AXER-204. AXER-204: human NoGo Trap fusion protein | 6 |
| Part 1 - AXER-204 - 30 mg Part 1 Open-label single ascending dose. Participants received a single dose of AXER-204. AXER-204: human NoGo Trap fusion protein | 6 |
| Part 1 - AXER-204 - 90 mg Part 1 Open-label single ascending dose. Participants received a single dose of AXER-204. AXER-204: human NoGo Trap fusion protein | 6 |
| Part 1 - AXER-204 - 200 mg Part 1 Open-label single ascending dose. Participants received a single dose of AXER-204. AXER-204: human NoGo Trap fusion protein | 6 |
| Part 2 - AXER-204 - 200 mg Part 2 Double-blind, placebo-controlled repeat dose. Participants received up to 6 doses given approximately every 21 days. AXER-204: human NoGo Trap fusion protein | 14 |
| Part 2 - Placebo Part 2 Double-blind, placebo-controlled repeat dose. Participants received up to 6 doses given approximately every 21 days. Placebo: Phosphate buffered saline formulation | 13 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | COVID-19 travel restrictions | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Unsuccessful lumbar puncture | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1 - AXER-204 - 30 mg | Total | Part 2 - Placebo | Part 2 - AXER-204 - 200 mg | Part 1 - AXER-204 - 3 mg | Part 1 - AXER-204 - 200 mg | Part 1 - AXER-204 - 90 mg |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 00 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 50 Participants | 12 Participants | 14 Participants | 6 Participants | 6 Participants | 6 Participants |
| Age, Continuous | 44.8 years STANDARD_DEVIATION 11.5 | 38.3 years STANDARD_DEVIATION 13.5 | 34.5 years STANDARD_DEVIATION 13.2 | 41.1 years STANDARD_DEVIATION 13.8 | 31.7 years STANDARD_DEVIATION 9.1 | 41.2 years STANDARD_DEVIATION 16.2 | 37.3 years STANDARD_DEVIATION 16 |
| Graded Redefined Assessment of Strength, Sensibility, and Prehension; Bilateral Prehension Performan | 21.0 units on a scale STANDARD_DEVIATION 7.6 | 17.7 units on a scale STANDARD_DEVIATION 5.4 | 18.5 units on a scale STANDARD_DEVIATION 4.5 | 16.4 units on a scale STANDARD_DEVIATION 3.8 | 16.5 units on a scale STANDARD_DEVIATION 5.8 | 16.3 units on a scale STANDARD_DEVIATION 6.7 | 18.0 units on a scale STANDARD_DEVIATION 6.3 |
| International Standards for the Neurological Classification of Spinal Cord Injury, Bilateral Upper E | 26.7 units on a scale STANDARD_DEVIATION 6.3 | 26.1 units on a scale STANDARD_DEVIATION 5.6 | 23.9 units on a scale STANDARD_DEVIATION 5.6 | 26.6 units on a scale STANDARD_DEVIATION 5.4 | 24.2 units on a scale STANDARD_DEVIATION 6.6 | 28.7 units on a scale STANDARD_DEVIATION 4.8 | 28.0 units on a scale STANDARD_DEVIATION 5.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 7 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 41 Participants | 11 Participants | 12 Participants | 3 Participants | 5 Participants | 5 Participants |
| Region of Enrollment United States | 6 participants | 51 participants | 13 participants | 14 participants | 6 participants | 6 participants | 6 participants |
| Sex: Female, Male Female | 0 Participants | 10 Participants | 3 Participants | 1 Participants | 1 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 41 Participants | 10 Participants | 13 Participants | 5 Participants | 2 Participants | 5 Participants |
| Spinal Cord Independence Measure, Version III; Self-care | 8.5 units on a scale STANDARD_DEVIATION 4.7 | 10.4 units on a scale STANDARD_DEVIATION 4.4 | 11 units on a scale STANDARD_DEVIATION 3.6 | 10.4 units on a scale STANDARD_DEVIATION 5.7 | 9.8 units on a scale STANDARD_DEVIATION 5 | 10.3 units on a scale STANDARD_DEVIATION 3.6 | 11.5 units on a scale STANDARD_DEVIATION 2.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 14 | 0 / 13 |
| other Total, other adverse events | 5 / 6 | 4 / 6 | 5 / 6 | 6 / 6 | 14 / 14 | 10 / 13 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 4 / 14 | 2 / 13 |
Outcome results
Primary
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.
Population: In Part 2, only pharmacokinetic samples from participants receiving AXER-204 were analyzed (n=14).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - AXER-204 - 3 mg | Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in CSF | 57200 h*ng/mL | Standard Deviation 61500 |
| Part 1 - AXER-204 - 30 mg | Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in CSF | 5810000 h*ng/mL | Standard Deviation 12300000 |
| Part 1 - AXER-204 - 90 mg | Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in CSF | 12500000 h*ng/mL | Standard Deviation 18000000 |
| Part 1 - AXER-204 - 200 mg | Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in CSF | 10000000 h*ng/mL | Standard Deviation 6260000 |
| Part 2 - AXER-204 - 200 mg | Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in CSF | NA h*ng/mL | — |
Primary
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.
Population: In Part 2, only pharmacokinetic samples from participants receiving AXER-204 were analyzed (n=14).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - AXER-204 - 3 mg | Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in Serum | NA h*ng/mL | — |
| Part 1 - AXER-204 - 30 mg | Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in Serum | NA h*ng/mL | — |
| Part 1 - AXER-204 - 90 mg | Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in Serum | 3670 h*ng/mL | Standard Deviation 1520 |
| Part 1 - AXER-204 - 200 mg | Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in Serum | 20900 h*ng/mL | Standard Deviation 7540 |
| Part 2 - AXER-204 - 200 mg | Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in Serum | NA h*ng/mL | — |
Primary
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
Population: In Part 2, only pharmacokinetic samples from participants receiving AXER-204 were analyzed (n=14).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - AXER-204 - 3 mg | Clearance From Serum | NA L/h | — |
| Part 1 - AXER-204 - 30 mg | Clearance From Serum | NA L/h | — |
| Part 1 - AXER-204 - 90 mg | Clearance From Serum | NA L/h | — |
| Part 1 - AXER-204 - 200 mg | Clearance From Serum | 4.84 L/h | Standard Deviation 1.41 |
| Part 2 - AXER-204 - 200 mg | Clearance From Serum | NA L/h | — |
Primary
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.
Population: In Part 2, only pharmacokinetic samples from participants receiving AXER-204 were analyzed (n=14)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - AXER-204 - 3 mg | Cmax in Serum | NA ng/mL | — |
| Part 1 - AXER-204 - 30 mg | Cmax in Serum | NA ng/mL | — |
| Part 1 - AXER-204 - 90 mg | Cmax in Serum | 277 ng/mL | Standard Deviation 79.1 |
| Part 1 - AXER-204 - 200 mg | Cmax in Serum | 641 ng/mL | Standard Deviation 173 |
| Part 2 - AXER-204 - 200 mg | Cmax in Serum | NA ng/mL | — |
Primary
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.
Population: In Part 2, only pharmacokinetic samples from participants receiving AXER-204 were analyzed (n=14).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - AXER-204 - 3 mg | Cmax of AXER-204 in CSF | 3340 ng/mL | Standard Deviation 2890 |
| Part 1 - AXER-204 - 30 mg | Cmax of AXER-204 in CSF | 87900 ng/mL | Standard Deviation 128000 |
| Part 1 - AXER-204 - 90 mg | Cmax of AXER-204 in CSF | 280000 ng/mL | Standard Deviation 221000 |
| Part 1 - AXER-204 - 200 mg | Cmax of AXER-204 in CSF | 412000 ng/mL | Standard Deviation 129000 |
| Part 2 - AXER-204 - 200 mg | Cmax of AXER-204 in CSF | NA ng/mL | — |
Primary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 - AXER-204 - 3 mg | Incidence of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | 5 Participants |
| Part 1 - AXER-204 - 30 mg | Incidence of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | 4 Participants |
| Part 1 - AXER-204 - 90 mg | Incidence of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | 5 Participants |
| Part 1 - AXER-204 - 200 mg | Incidence of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | 6 Participants |
| Part 2 - AXER-204 - 200 mg | Incidence of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | 14 Participants |
| Part 2 - Placebo | Incidence of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | 10 Participants |
Primary
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.
Population: In Part 2, only pharmacokinetic samples from participants receiving AXER-204 were analyzed (n=14).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - AXER-204 - 3 mg | t1/2 in Serum | NA hours | — |
| Part 1 - AXER-204 - 30 mg | t1/2 in Serum | NA hours | — |
| Part 1 - AXER-204 - 90 mg | t1/2 in Serum | NA hours | — |
| Part 1 - AXER-204 - 200 mg | t1/2 in Serum | 53.9 hours | Standard Deviation 24.8 |
| Part 2 - AXER-204 - 200 mg | t1/2 in Serum | NA hours | — |
Primary
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.
Population: In Part 2, only pharmacokinetic samples from participants receiving AXER-204 were analyzed (n=14).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - AXER-204 - 3 mg | t1/2 of AXER-204 in CSF | NA h | — |
| Part 1 - AXER-204 - 30 mg | t1/2 of AXER-204 in CSF | 23.1 h | Standard Deviation 32.2 |
| Part 1 - AXER-204 - 90 mg | t1/2 of AXER-204 in CSF | 13.5 h | Standard Deviation 10.8 |
| Part 1 - AXER-204 - 200 mg | t1/2 of AXER-204 in CSF | 12.5 h | Standard Deviation 7.08 |
| Part 2 - AXER-204 - 200 mg | t1/2 of AXER-204 in CSF | NA h | — |
Primary
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.
Population: In Part 2, only pharmacokinetic samples from participants receiving AXER-204 were analyzed (n=14).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - AXER-204 - 3 mg | Tmax in Serum | NA hours | — |
| Part 1 - AXER-204 - 30 mg | Tmax in Serum | NA hours | — |
| Part 1 - AXER-204 - 90 mg | Tmax in Serum | 16.8 hours | Standard Deviation 6.5 |
| Part 1 - AXER-204 - 200 mg | Tmax in Serum | 12.8 hours | Standard Deviation 5.06 |
| Part 2 - AXER-204 - 200 mg | Tmax in Serum | NA hours | — |
Primary
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.
Population: In Part 2, only pharmacokinetic samples from participants receiving AXER-204 were analyzed (n=14).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - AXER-204 - 3 mg | Tmax of AXER-204 in CSF | 24.2 h | Standard Deviation 0.91 |
| Part 1 - AXER-204 - 30 mg | Tmax of AXER-204 in CSF | 23.9 h | Standard Deviation 0.89 |
| Part 1 - AXER-204 - 90 mg | Tmax of AXER-204 in CSF | 23.2 h | Standard Deviation 0.49 |
| Part 1 - AXER-204 - 200 mg | Tmax of AXER-204 in CSF | 22.9 h | Standard Deviation 0.93 |
| Part 2 - AXER-204 - 200 mg | Tmax of AXER-204 in CSF | NA h | — |
Primary
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.
Population: In Part 2, only pharmacokinetic samples from participants receiving AXER-204 were analyzed (n=14).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 - AXER-204 - 3 mg | Volume of Distribution | NA L | — |
| Part 1 - AXER-204 - 30 mg | Volume of Distribution | NA L | — |
| Part 1 - AXER-204 - 90 mg | Volume of Distribution | NA L | — |
| Part 1 - AXER-204 - 200 mg | Volume of Distribution | 344 L | Standard Deviation 70.1 |
| Part 2 - AXER-204 - 200 mg | Volume of Distribution | NA L | — |
Secondary
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
Population: This was pre-specified to be an exploratory outcome in Part 1, and therefore data will not be reported
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1 - AXER-204 - 3 mg | Change in Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) Bilateral Prehension Performance Score | 0.42 score on a scale |
| Part 1 - AXER-204 - 30 mg | Change in Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) Bilateral Prehension Performance Score | 1.97 score on a scale |
p-value: 0.1395% CI: [-3.62, 0.5]Mixed Models Analysis
Secondary
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
Population: This was pre-specified to be an exploratory outcome in Part 1, and therefore data will not be reported
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1 - AXER-204 - 3 mg | Change in International Standards for Neurological Classification of SCI (ISNCSCI) Bilateral Upper Extremity Motor Score (UEMS) | 2.05 score on a scale |
| Part 1 - AXER-204 - 30 mg | Change in International Standards for Neurological Classification of SCI (ISNCSCI) Bilateral Upper Extremity Motor Score (UEMS) | 1.52 score on a scale |
p-value: 0.5995% CI: [-1.48, 2.55]Mixed Models Analysis
Secondary
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
Population: This was pre-specified to be an exploratory outcome in Part 1, and therefore data will not be reported
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1 - AXER-204 - 3 mg | Change in Version III of the Spinal Cord Independence Measure (SCIM III) Self-care | -0.25 score on a scale |
| Part 1 - AXER-204 - 30 mg | Change in Version III of the Spinal Cord Independence Measure (SCIM III) Self-care | 0.91 score on a scale |
p-value: 0.1695% CI: [-2.81, 0.5]Mixed Models Analysis
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 - AXER-204 - 3 mg | Patient Global Impression of Change (PGIC) Responder Rate | NA Participants |
| Part 1 - AXER-204 - 30 mg | Patient Global Impression of Change (PGIC) Responder Rate | NA Participants |
| Part 1 - AXER-204 - 90 mg | Patient Global Impression of Change (PGIC) Responder Rate | NA Participants |
| Part 1 - AXER-204 - 200 mg | Patient Global Impression of Change (PGIC) Responder Rate | NA Participants |
| Part 2 - AXER-204 - 200 mg | Patient Global Impression of Change (PGIC) Responder Rate | 3 Participants |
| Part 2 - Placebo | Patient Global Impression of Change (PGIC) Responder Rate | 4 Participants |
p-value: 0.6895% CI: [-43.3, 25.4]Fisher Exact