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

• ClinicalTrials.gov Identifier: NCT03989440
• Recruitment Status: Recruiting
• First Posted: June 18, 2019
• Last Update Posted: August 13, 2019
• Sponsor: ReNetX Bio, Inc.
• Information provided by (Responsible Party): ReNetX Bio, Inc.

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.

Condition or disease	Intervention/treatment	Phase
Chronic Spinal Cord Injury	Drug: AXER-204; Drug: Placebo	Phase 1; Phase 2

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. Up to 42 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Part 1 is open-label single-ascending dose. Part 2 is double-blind, placebo-controlled, repeat dose.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Part 1 - None; Part 2 - Quadruple
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: July 16, 2019
• Estimated Primary Completion Date: July 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: AXER-204; Part 1 - Single ascending doses; Part 2 - Repeated dose	Drug: AXER-204; human NoGo Trap fusion protein; Other Names: human NoGo Trap; human Nogo Receptor decoy
Placebo Comparator: Placebo; Part 2 only - Repeated dose	Drug: Placebo; Phosphate buffered saline formulation

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 Post-dose to 28-days after last dose ]
   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.
2. Area Under the Concentration-Time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of AXER-204 [ Time Frame: Day 1 pre-dose up to Day 29 ]
   AXER-204 will be measured in cerebrospinal fluid (CSF) and in serum
3. Change in International Standards for Neurological Classification of SCI (ISNCSCI) Upper Extremity Motor Score (UEMS) [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
   The ISNCSCI scale includes a Motor and Sensory examination for each side of the body (left/right). The Sensory examination involves 'light touch' and 'pinprick' for each dermatome (28) on both sides of the body (total 56). A score of 0, 1 or 2 can be given to each dermatome resulting in a total max. of 112 points. The Motor level is determined by examining the muscle function within each of the 10 myotomes on each side of the body (20 myotomes in total). A score ranging from 1 to 5 can be given to each myotome tested resulting in a maximum score of 100 (50 for upper extremity and 50 for lower extremity). Higher values indicate better function with the maximum scores corresponding to normal function.

Secondary Outcome Measures :

1. Change in International Standards for Neurological Classification of SCI (ISNCSCI) motor and sensory scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
   The ISNCSCI scale includes a Motor and Sensory examination for each side of the body (left/right). The Sensory examination involves 'light touch' and 'pinprick' for each dermatome (28) on both sides of the body (total 56). A score of 0, 1 or 2 can be given to each dermatome resulting in a total max. of 112 points. The Motor level is determined by examining the muscle function within each of the 10 myotomes on each side of the body (20 myotomes in total). A score ranging from 1 to 5 can be given to each myotome tested resulting in a maximum score of 100 (50 for upper extremity and 50 for lower extremity). Higher values indicate better function with the maximum scores corresponding to normal function.
2. Change in Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
   The GRASSP is a clinical impairment measure for the upper limb for use after tetraplegia. The measure includes domains which are important in describing hand function: Strength with scores from 0-50 for each side, Sensory testing with scores ranging from 0-12 for each hand, Prehension ability with scores 0-12 for each hand, and Prehension performance with scores from 0-30 for each hand. Higher subscores indicate better function.
3. Change in version III of the Spinal Cord Independence Measure (SCIM III) self-care and mobility domain scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
   The SCIM III is a questionnaire that assesses activities of daily living (ADL) regarding self-care, mobility, respiration, and sphincter management. The self-care and mobility domains have scores ranging from 0-20 and 0-40 respectively. Higher scores correspond to better ability to carry out ADL.
4. Change in Capabilities of Upper Extremity Test (CUE-T) scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
   The CUE-T is a clinical impairment measure for upper limb use after tetraplegia. The test has 19 items (17 unilateral and tested separately for the right and left upper extremities; two bilateral items) that are scored on a five-point scale (0-4) using one of three scoring dimensions (number of times task is completed; amount of weight; amount of time). The total assessment has a possible range in scores from 0 to 144. Higher scores correspond to better function.
5. Change in Capabilities of Upper Extremity Questionnaire (CUE-Q) scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
   The CUE-Q is a questionnaire to assess arm and hand function comprised of 17 questions with scores of 0-4 assigned to each side for each question resulting in a total score ranging from 0-136. A higher score corresponds to better function.
6. Change in SF - 36 v2 Health Survey scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
   The Short Form-36 is a 36-question, 8-domain survey designed to assess physical and emotional health. Raw scores can be converted to normalized values ranging from 0-100 for each domain. Each domain has a normal score of 50 with lower scores indicating progressively poorer health.
7. Change in Neuro-QOL Item Bank v1.0 - Upper Extremity Function questionnaire scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
   The Neuro-Quality of Life Item Bank v1.0 - Upper Extremity Function questionnaire consists of 20 questions focused on activities of activities of daily living (ADL) requiring use of arms and hands. Scores for each question range from 1-5 resulting in a total maximum score of 100. A higher score corresponds to greater ability to conduct ADL.

Other Outcome Measures:

1. Change in International Standards to document remaining Autonomic Function after Spinal Cord Injury (ISAFSCI) scores [ Time Frame: Screening to Day 169 or 28 days after last dose and 6 months after last dose ]
   The ISAFSCI consists of patient reported responses on remaining autonomic function regarding regulation of heart rate, blood pressure, sweating, body temperature, breathing, urinary function, bowel function, and sexual function. Scores are assigned as 2=normal, 1=reduced or altered, 0=complete loss of control, or NT=unable to assess for each item.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 12 points inclusive

3. Confirmation by MRI of the following:

   1. Chronic SCI (persistent spinal cord lesion)
   2. Retained spinal cord tissue spanning the lesion (ie, no imaging findings suggestive of anatomic transection)
   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.

Contacts and Locations

Contacts

Contact: George Maynard, PhD; 1-203-208-8925; info@renetx.com

Locations

United States, California

Keck Medicine of USC; Recruiting

Los Angeles, California, United States, 90033

Contact: Sandra Oviedo sandra.oviedo@med.usc.edu

Principal Investigator: Charles Liu, MD, PhD

United States, Georgia

Shepherd Center; Recruiting

Atlanta, Georgia, United States, 30309

Contact: Casey Kandilakis, PT,DPT,NCS casey.kandilakis@shepherd.org

Principal Investigator: Donald Leslie, MD

United States, Illinois

Shirley Ryan AbilityLab; Recruiting

Chicago, Illinois, United States, 60611

Contact: Sneha Solanki, MS 312-238-3647 ssolanki02@sralab.org

Principal Investigator: David Chen, MD

United States, Ohio

The Ohio State University Wexner Medical Center; Recruiting

Columbus, Ohio, United States, 43210

Contact: Amy Bartlett, BA, CCRC 614-366-9050 amy.bartlett@osumc.edu

Principal Investigator: Jan Schwab, MD, PhD

United States, Pennsylvania

Thomas Jefferson University; Recruiting

Philadelphia, Pennsylvania, United States, 19107

Contact: Marilyn Owens, RN, BSN 215-955-6579 marilyn.owens@jefferson.edu

Principal Investigator: Ralph Marino, MD

Sponsors and Collaborators

ReNetX Bio, Inc.

Investigators

• Study Director: ReNetX Bio; ReNetX Bio

More Information

• Responsible Party: ReNetX Bio, Inc.
• ClinicalTrials.gov Identifier: NCT03989440 History of Changes
• Other Study ID Numbers: RNX-AX204-101
• First Posted: June 18, 2019
• Last Update Posted: August 13, 2019
• Last Verified: July 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ReNetX Bio, Inc.:

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

Additional relevant MeSH terms:

Spinal Cord Injuries; Wounds and Injuries; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System