Chronic Spinal Cord Injury
Conditions
Keywords
Chronic Spinal Cord Injury, Cervical Spinal Cord Injury, Tetraplegia
Brief summary
The goal of this clinical trial is to learn if NVG-291 can improve function in adults with chronic cervical motor-incomplete spinal cord injury. It will also learn about the safety of NVG-291. The main questions it aims to answer are: * Does NVG-291 improve hand function and daily activities? * What side effects do participants have when taking NVG-291? Researchers will compare NVG-291 to a placebo (a look-alike substance that does not contain NVG-291) to see if NVG-291 improves function in adults with chronic cervical motor-incomplete spinal cord injury. Participants will: * Take NVG-291 or a placebo by injection under the skin (subcutaneous) once daily for 12 weeks. * Attend clinic visits for checkups and safety tests. * Complete tests and questionnaires about hand function, walking, daily activities, and quality of life. * Take part in an interview about changes in their condition, within 14 days after the Week 12 visit.
Detailed description
NVG-291 is an investigational peptide therapeutic designed to promote nervous system repair by modulating pathways that may inhibit neural regeneration after spinal cord injury. Chronic cervical motor-incomplete spinal cord injury is associated with persistent impairments in upper-extremity function, mobility, independence, and quality of life, and there are currently no approved pharmacologic therapies specifically intended to promote neurological repair in this population. Previous nonclinical studies and an earlier randomized clinical study of NVG-291 provided evidence supporting further evaluation of its potential to improve neurological connectivity and functional recovery in individuals with chronic cervical motor incomplete spinal cord injury. RESTORE (NVG-291-301) is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy, safety, and pharmacokinetics of NVG-291 in adults with chronic cervical motor incomplete spinal cord injury. Approximately 150 participants will be enrolled at up to 60 sites in the United States and Canada and randomized in a 1:1 ratio to receive either NVG-291 or placebo. Randomization will be stratified by country and baseline injury severity category. Participants will receive once-daily subcutaneous administration of study treatment for 12 weeks, followed by a 4-week noninterventional follow-up period. The study is designed to assess treatment effects after completion of the dosing period and to evaluate whether any observed functional changes persist following treatment discontinuation. Primary analysis will be performed at Week 12, with follow-up through Week 16. In addition to efficacy and safety assessments, the study will characterize the population pharmacokinetics of NVG-291 in a subset of participants receiving NVG-291, and will evaluate patient-reported outcomes, functional measures, quality-of-life assessments, and exploratory measures intended to further characterize the potential effects of NVG-291 on recovery following spinal cord injury. An optional open-label extension study may be offered following completion of the main study to provide access to NVG-291 for participants originally assigned to placebo.
Interventions
DRUGNVG-291
NVG-291 is an investigational peptide therapeutic administered by subcutaneous injection. Participants randomized to the experimental arm will receive NVG-291 once daily for 12 weeks. NVG-291 is designed to promote nervous system repair and functional recovery following chronic spinal cord injury.
DRUGPlacebo
Matching placebo is supplied as a sterile lyophilized formulation matching NVG-291 in appearance and route of administration. Participants randomized to the placebo arm will receive placebo once daily by subcutaneous injection for 12 weeks.
Sponsors
NervGen Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
All subjects, investigators, and study personnel involved in the conduct of the study, including data management, will be blinded to treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Provide written informed consent prior to any study-specific procedures. 2. Be 18 to 75 years of age, inclusive. 3. Have chronic cervical spinal cord injury resulting from acute traumatic injury occurring 1 to 10 years prior to randomization. 4. Have motor-incomplete cervical spinal cord injury as determined by International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) assessment at screening, meeting all of the following: American Spinal Injury Association (ASIA) Impairment Scale grade C or D; motor level at C7 or rostral on both the right and the left side; and a muscle grade of 1 or greater on ISNCSCI manual muscle testing in at least one lower-extremity key muscle function (L2 to S1) on either side. 5. Have documented traumatic spinal cord injury confirmed by historical and/or current magnetic resonance imaging (MRI) or computed tomography (CT). 6. Have a Walking Index for Spinal Cord Injury II (WISCI II) score of 0 to 14, inclusive. 7. Have a score of at least 2 on at least one GRASSP Prehension Ability grasp pattern (cylindrical grasp, lateral key pinch, or tip-to-tip pinch) in at least one upper extremity, no more than one grasp-pattern score of 4 in the qualifying upper extremity, and a combined (bilateral) GRASSP Quantitative Prehension score no greater than 34, of a possible 40, across the sum of the four Prehension Performance task scores for the right and left hand. 8. Be willing and able to comply with study visits, assessments, study procedures, and study drug administration requirements. 9. Female participants of childbearing potential and male participants must agree to use protocol-specified contraception during study participation.
Exclusion criteria
1. Nontraumatic spinal cord injury, penetrating spinal cord injury, multiple noncontiguous spinal cord lesions, or anatomically complete spinal cord transection. 2. Ventilatory dependence, defined as invasive mechanical ventilation via tracheostomy, noninvasive ventilation for chronic respiratory failure, or diaphragmatic or phrenic nerve pacing. Continuous or automatic positive airway pressure (CPAP/APAP) used solely for obstructive sleep apnea is not exclusionary. 3. Any condition preventing adequate assessment of all four extremities. 4. Any neurological condition that could interfere with study assessments or interpretation of results, including multiple sclerosis, stroke, amyotrophic lateral sclerosis, dementia, or progressive syringomyelia. 5. History of uncontrolled seizures or any seizure within 6 months prior to screening. 6. Pregnant or breastfeeding. 7. History of substance abuse within 12 months prior to screening. 8. Evidence of spinal instability, persistent spinal stenosis, or spinal cord compression related to the original injury. 9. Prior treatment with central nervous system gene therapy. Prior treatment with a protein tyrosine phosphatase sigma (PTPσ) mimetic peptide. Stem cell or cell therapy within 12 months prior to screening. 10. Severe neuropathic pain inadequately controlled by medication. 11. Body mass index (BMI) \>40 kg/m². 12. Known hypersensitivity to cetirizine, mannitol, trehalose, or polysorbate 80. 13. Receipt of botulinum toxin injection within 6 months prior to screening or 4-aminopyridine within 7 days prior to first dose. Current intrathecal opioid use. 14. Current participation in another interventional clinical trial or prior exposure to NVG-291. 15. Receipt of prohibited medications or therapies intended to enhance neuroplasticity within protocol-defined restricted periods. 16. Presence of an implanted neurostimulation or brain-computer interface device, or current neurostimulation therapy, including spinal cord stimulation, neuromuscular stimulation, vagal nerve stimulation, or phrenic nerve stimulation. 17. Malignancy within 5 years prior to screening, except adequately treated non-melanoma skin cancer or cervical or breast carcinoma in situ. 18. Clinically significant hepatic disease, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 × upper limit of normal, or severe renal impairment (estimated glomerular filtration rate \<30 mL/min/1.73 m²). 19. Any disease, injury, medical condition, social condition, or behavioral condition that could interfere with study participation, study assessments, interpretation of results, or compliance with study requirements, in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of NVG-291 as measured by change from baseline in combined Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) Quantitative Prehension (QtP) score | Baseline to Week 12 | Change from baseline to Week 12 in the combined GRASSP QtP score. The combined GRASSP QtP score is the sum of four Prehension Performance task scores for the right and the left hand and ranges from 0 to 40. A higher score on GRASSP QtP indicates improved prehension performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of NVG-291 as assessed by change from baseline in heart rate | Baseline through Week 16 | Change from baseline in heart rate (beats/minute). |
| Safety and tolerability of NVG-291 as assessed by change from screening in body weight | Screening through Week 16 | Change from screening in body weight (kg). |
| Safety and tolerability of NVG-291 as assessed by change from baseline in body temperature | Baseline through Week 16 | Change from baseline in body temperature (°C). |
| Safety and tolerability of NVG-291 as assessed by the number of participants with clinically significant electrocardiogram abnormalities | Baseline through Week 16 | Number of participants with clinically significant electrocardiogram (ECG) abnormalities. |
| Pharmacokinetics of NVG-291 as measured by plasma NVG-291 concentration | Day 1 Through Week 12 | Plasma NVG-291 concentration (ng/mL) in participants randomized to NVG-291 who are included in the pharmacokinetic subset. Samples are collected pre-dose, 30 minutes post-dose, and 3 hours post-dose at each specified visit, to support a population pharmacokinetic (PopPK) analysis. |
| Efficacy of NVG-291 as measured by change at Week 12 in Patient Global Impression of Change (PGIC) | Week 12 | Patient Global Impression of Change (PGIC) at Week 12. The PGIC is a single-item, patient-reported measure of perception of change in condition, scored on a 7-point scale from 1 (very much worse) to 7 (very much improved). Higher scores indicate greater improvement. |
| Efficacy of NVG-291 as measured by change at Week 12 in Clinician Global Impression of Change (CGIC) | Week 12 | The CGIC is a single-item, clinician-reported measure of change in condition, scored on a 7-point scale from 1 (very much worse) to 7 (very much improved). Higher scores indicate greater improvement. |
| Efficacy of NVG-291 as measured by change from baseline in Spinal Cord Independence Measure Version III (SCIM-III) | Baseline to Week 12 | Change from baseline to Week 12 in the Spinal Cord Independence Measure, Version III (SCIM-III) total score. The SCIM-III total score ranges from 0 to 100. Higher scores indicate greater functional independence. |
| Efficacy of NVG-291 as measured by change from baseline in Modified Ashworth Scale (MAS) score | Baseline to Week 12 | Change from baseline to Week 12 in the Modified Ashworth Scale (MAS) total score, the sum of scores for the quadriceps femoris, hamstrings, and soleus assessed bilaterally. Total scores range from 0 to 30. Higher scores indicate more severe spasticity. |
| Participant-perceived meaningfulness of change assessed by the patient-reported outcome (PRO) Qualitative Interview | Within 14 days after the Week 12 visit | Patient-reported perception of change from baseline at Week 12, assessed by a semi-structured qualitative interview conducted within 14 days after the Week 12 visit. The interview is not a scored scale and has no minimum or maximum value. Transcripts are coded against a prespecified analysis framework, and results will be reported as the number and percentage of participants reporting meaningful improvement in each prespecified concept. |
| Efficacy of NVG-291 as measured by change from baseline in 10 Meter Walk Test (10mWT) | Baseline to Week 12 | Change from baseline to Week 12 in walking velocity (meters/second) measured by the 10 Meter Walk Test (10mWT). Higher walking velocity indicates better performance. |
| Efficacy of NVG-291 as measured by change from baseline in combined GRASSP Total Score | Baseline to Week 12 | Change from baseline to Week 12 in the combined GRASSP Total score, the sum of the strength, sensibility, and prehension domain scores for the right and the left hand. The combined GRASSP Total score ranges from 0 to 188. Higher scores indicate better upper-extremity function. |
| Efficacy of NVG-291 as measured by change from baseline in Clinician Global Impression of Severity (CGIS) | Baseline to Week 12 | Change from baseline to Week 12 in the Clinician Global Impression of Severity (CGIS) score. The CGIS is a single-item, clinician-rated measure of overall severity, scored on a 7-point scale from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicate greater severity. |
| Efficacy of NVG-291 as measured by change from baseline in Patient Global Impression of Severity (PGIS) | Baseline to Week 12 | Change from baseline to Week 12 in the Patient Global Impression of Severity (PGIS) score. The PGIS is a single-item, participant-rated measure of overall severity, scored on a 5-point scale from 1 (none) to 5 (very severe). Higher scores indicate greater severity. |
| Safety and tolerability of NVG-291 as assessed by the incidence of adverse events (AEs) | Informed consent through Week 16 | Incidence of AEs. |
| Safety and tolerability of NVG-291 as assessed by the incidence of serious adverse events (SAEs) | Informed consent through Week 16 | Incidence of SAEs. |
| Safety and tolerability of NVG-291 as assessed by the number of participants with clinically significant laboratory abnormalities | Baseline through Week 16 | Number of participants with clinically significant abnormalities in clinical laboratory assessments. |
| Safety and tolerability of NVG-291 as assessed by change from baseline in diastolic blood pressure | Baseline through Week 16 | Change from baseline in diastolic blood pressure (mmHg). |
| Safety and tolerability of NVG-291 as assessed by change from baseline in systolic blood pressure | Baseline through Week 16 | Change from baseline in systolic blood pressure (mmHg). |
Countries
Canada, United States
Contacts
CONTACTStudy Team
CONTACTAdam Rogers MD, Chief Executive Officer, NervGen Pharma
Outcome results
None listed