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Chronic Spinal Cord InjuryPhase 1/2RESETNCT03989440

AXER-204 in Participants With Chronic Spinal Cord Injury

A Phase 1/2 study testing AXER-204 in people with Chronic Spinal Cord Injury, run by ReNetX Bio, Inc. at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Chronic Spinal Cord Injury
What is being tested?
AXER-204
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
52 participants
Where
6 sitesUnited States
Study dates
16 Jul 2019to 21 Jun 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites
  • Shepherd Center

    Atlanta, Georgia, 30309

  • Spaulding Rehabilitation

    Boston, Massachusetts, 02129

  • Shirley Ryan AbilityLab / Northwestern

    Chicago, Illinois, 60611

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • Keck Medicine of USC

    Los Angeles, California, 90033

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
AXER-204, Placebo
Keywords
myelin-associated inhibitor, Nogo-A, MAG, OMgp, Nogo Receptor

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AXER-204Drug

    Also called human NoGo Trap, human Nogo Receptor decoy

    human NoGo Trap fusion protein

  • PlaceboDrug

    Phosphate buffered saline formulation

Study groups in NCT03989440
Study groupRoleWhat they receive
AXER-204ExperimentalPart 1 - Single ascending doses; Part 2 - Repeated dose
Receives: Drug: AXER-204
PlaceboPlacebo comparatorPart 2 only - Repeated dose
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in Serum

    Measured: 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.

  3. Cmax in Serum

    Measured: 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.

  4. Tmax in Serum

    Measured: 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.

  5. t1/2 in Serum

    Measured: 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.

  6. Clearance From Serum

    Measured: Day 1 pre-dose up to Day 29 in Part 1, Pre-dose up to Day 253 in Part 2

  7. Volume of Distribution

    Volume of distribution calculated from serum exposure data

    Measured: 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.

  8. Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 in CSF

    Measured: 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.

  9. Cmax of AXER-204 in CSF

    Measured: 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.

  10. Tmax of AXER-204 in CSF

    Measured: 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.

  11. t1/2 of AXER-204 in CSF

    Measured: 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)
  1. 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.

    Measured: Baseline to Day 169

  2. 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.

    Measured: Baseline to Day 169

  3. 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.

    Measured: Baseline to Day 169

  4. 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.

    Measured: Day 169

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jun 2019
  2. Study start16 Jul 2019
  3. Primary completion21 Jun 2022
  4. Study completion21 Jun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Part 1 is open-label single-ascending dose. Part 2 is double-blind, placebo-controlled, repeat dose.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03989440
Sponsor's protocol ID
RNX-AX204-101
Acronym
RESET
Status last verified
Jul 2023
First submitted
11 Jun 2019
Last updated
22 Aug 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 37479373

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AXER-204 in people with Chronic Spinal Cord Injury, run by ReNetX Bio, Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Up to Day 29 for Part 1 and Day 253 for Part 2). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03989440, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2023.

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