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AXER-204 in Participants With Chronic Spinal Cord Injury (RESET)

Primary Purpose

Chronic Spinal Cord Injury

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AXER-204
Placebo
Sponsored by
ReNetX Bio, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Spinal Cord Injury focused on measuring myelin-associated inhibitor, Nogo-A, MAG, OMgp, Nogo Receptor

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Keck Medicine of USC
  • Shepherd Center
  • Shirley Ryan AbilityLab / Northwestern
  • Spaulding Rehabilitation
  • The Ohio State University Wexner Medical Center
  • Thomas Jefferson University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AXER-204

Placebo

Arm Description

Part 1 - Single ascending doses; Part 2 - Repeated dose

Part 2 only - Repeated dose

Outcomes

Primary Outcome Measures

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.
Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in Serum
Cmax in Serum
Tmax in Serum
t1/2 in Serum
Clearance From Serum
Volume of Distribution
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
Cmax of AXER-204 in CSF
Tmax of AXER-204 in CSF
t1/2 of AXER-204 in CSF

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
June 11, 2019
Last Updated
July 28, 2023
Sponsor
ReNetX Bio, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03989440
Brief Title
AXER-204 in Participants With Chronic Spinal Cord Injury
Acronym
RESET
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
July 16, 2019 (Actual)
Primary Completion Date
June 21, 2022 (Actual)
Study Completion Date
June 21, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ReNetX Bio, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Spinal Cord Injury
Keywords
myelin-associated inhibitor, Nogo-A, MAG, OMgp, Nogo Receptor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Part 1 is open-label single-ascending dose. Part 2 is double-blind, placebo-controlled, repeat dose.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Part 1 - None; Part 2 - Quadruple
Allocation
Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AXER-204
Arm Type
Experimental
Arm Description
Part 1 - Single ascending doses; Part 2 - Repeated dose
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Part 2 only - Repeated dose
Intervention Type
Drug
Intervention Name(s)
AXER-204
Other Intervention Name(s)
human NoGo Trap, human Nogo Receptor decoy
Intervention Description
human NoGo Trap fusion protein
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Phosphate buffered saline formulation
Primary Outcome Measure Information:
Title
Incidence of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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
Title
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.
Title
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.
Title
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.
Title
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.
Title
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
Title
Volume of Distribution
Description
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.
Title
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.
Title
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.
Title
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.
Title
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.
Secondary Outcome Measure Information:
Title
Change in International Standards for Neurological Classification of SCI (ISNCSCI) Bilateral Upper Extremity Motor Score (UEMS)
Description
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
Title
Change in Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) Bilateral Prehension Performance Score
Description
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
Title
Change in Version III of the Spinal Cord Independence Measure (SCIM III) Self-care
Description
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
Title
Patient Global Impression of Change (PGIC) Responder Rate
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
George Maynard, PhD
Organizational Affiliation
ReNetX Bio
Official's Role
Study Director
Facility Information:
Facility Name
Keck Medicine of USC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Shepherd Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Shirley Ryan AbilityLab / Northwestern
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Spaulding Rehabilitation
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02129
Country
United States
Facility Name
The Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States

12. IPD Sharing Statement

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AXER-204 in Participants With Chronic Spinal Cord Injury

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