AXER-204 in Participants With Chronic Spinal Cord Injury

NCT03989440 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: RNX-AX204-101
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 6

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.

Conditions

Chronic Spinal Cord Injury

Keywords

myelin-associated inhibitor; Nogo-A; MAG; OMgp; Nogo Receptor

Outcome Measures

Primary Outcomes (11)

• 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.

  Up to Day 29 for Part 1 and Day 253 for Part 2

• 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

• Volume of Distribution

  Volume of distribution calculated from serum exposure data

  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.

• 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.

• 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.

Secondary Outcomes (4)

• Change in International Standards for Neurological Classification of SCI (ISNCSCI) Bilateral Upper Extremity Motor Score (UEMS)

  Baseline to Day 169

• Change in Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) Bilateral Prehension Performance Score

  Baseline to Day 169

• Change in Version III of the Spinal Cord Independence Measure (SCIM III) Self-care

  Baseline to Day 169

• Patient Global Impression of Change (PGIC) Responder Rate

  Day 169

Study Arms (2)

AXER-204

EXPERIMENTAL

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

Drug: AXER-204

Placebo

PLACEBO COMPARATOR

Part 2 only - Repeated dose

Drug: Placebo

Interventions

AXER-204 DRUG

human NoGo Trap fusion protein

Also known as: human NoGo Trap, human Nogo Receptor decoy

AXER-204

Placebo DRUG

Phosphate buffered saline formulation

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• ReNetX Bio, Inc.: lead

Study Sites (6)

Keck Medicine of USC

Los Angeles, California, 90033, United States

Location

Shepherd Center

Atlanta, Georgia, 30309, United States

Location

Shirley Ryan AbilityLab / Northwestern

Chicago, Illinois, 60611, United States

Location

Spaulding Rehabilitation

Boston, Massachusetts, 02129, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• Maynard G, Kannan R, Liu J, Wang W, Lam TKT, Wang X, Adamson C, Hackett C, Schwab JM, Liu C, Leslie DP, Chen D, Marino R, Zafonte R, Flanders A, Block G, Smith E, Strittmatter SM. Soluble Nogo-Receptor-Fc decoy (AXER-204) in patients with chronic cervical spinal cord injury in the USA: a first-in-human and randomised clinical trial. Lancet Neurol. 2023 Aug;22(8):672-684. doi: 10.1016/S1474-4422(23)00215-6.

  PMID: 37479373 DERIVED

Results Point of Contact

• Title: George D. Maynard, Ph.D., Study Director
• Organization: ReNetX Bio, Inc.

info@renetx.com

2032088925

Study Officials

• George Maynard, PhD

  ReNetX Bio

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part 1 - None; Part 2 - Quadruple
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 is open-label single-ascending dose. Part 2 is double-blind, placebo-controlled, repeat dose.

Study Record Dates

• First Submitted: June 11, 2019
• First Posted: June 18, 2019
• Study Start: July 16, 2019
• Primary Completion: June 21, 2022
• Study Completion: June 21, 2022
• Last Updated: August 22, 2023
• Results First Posted: August 22, 2023

Record last verified: 2023-07

Locations

US (6)