Clinical trial NCT03989440: AXER-204 in Participants With Chronic Spinal Cord Injury
Official title: A Multicenter, Two Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AXER-204 in Subjects With Chronic Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Spinal Cord Injury
Keywords: myelin-associated inhibitor
Nogo-A
MAG
OMgp
Nogo Receptor
Lead sponsor: ReNetX Bio, Inc.
Sponsor class: INDUSTRY
First posted: 2019-06-18
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1 is open-label single-ascending dose. Part 2 is double-blind, placebo-controlled, repeat dose.
Primary purpose: TREATMENT

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.

Eligibility 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/Exclusion criteria may apply.

Primary outcomes:
measure: Incidence of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Day 29 for Part 1 and Day 253 for Part 2
measure: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in Serum
timeFrame: 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.
measure: Cmax in Serum
timeFrame: 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.
measure: Tmax in Serum
timeFrame: 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.
measure: t1/2 in Serum
timeFrame: 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.
measure: Clearance From Serum
timeFrame: Day 1 pre-dose up to Day 29 in Part 1, Pre-dose up to Day 253 in Part 2
measure: Volume of Distribution
timeFrame: 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.
measure: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in CSF
timeFrame: 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.
measure: Cmax of AXER-204 in CSF
timeFrame: 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.
measure: Tmax of AXER-204 in CSF
timeFrame: 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.
measure: t1/2 of AXER-204 in CSF
timeFrame: 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.
Secondary outcomes:
measure: Change in International Standards for Neurological Classification of SCI (ISNCSCI) Bilateral Upper Extremity Motor Score (UEMS)
timeFrame: Baseline to Day 169
measure: Change in Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) Bilateral Prehension Performance Score
timeFrame: Baseline to Day 169
measure: Change in Version III of the Spinal Cord Independence Measure (SCIM III) Self-care
timeFrame: Baseline to Day 169
measure: Patient Global Impression of Change (PGIC) Responder Rate
timeFrame: Day 169
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Keck Medicine of USC
state: California
city: Atlanta
country: United States
facility: Shepherd Center
state: Georgia
city: Chicago
country: United States
facility: Shirley Ryan AbilityLab / Northwestern
state: Illinois
city: Boston
country: United States
facility: Spaulding Rehabilitation
state: Massachusetts
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
Study officials:
affiliation: ReNetX Bio
name: George Maynard, PhD
role: STUDY_DIRECTOR
References: