A Trial Investigating the Efficacy and Safety of NVG-291 in Subjects With Chronic Spinal Cord Injury - A Randomized, Double-Blind, Placebo-Controlled Multicenter Phase 3 Trial (RESTORE)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 150
- 试验地点
- 18
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
All subjects, investigators, and study personnel involved in the conduct of the study, including data management, will be blinded to treatment.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide written informed consent prior to any study-specific procedures.
- •Be 18 to 75 years of age, inclusive.
- •Have chronic cervical spinal cord injury resulting from acute traumatic injury occurring 1 to 10 years prior to randomization.
- •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.
- •Have documented traumatic spinal cord injury confirmed by historical and/or current magnetic resonance imaging (MRI) or computed tomography (CT).
- •Have a Walking Index for Spinal Cord Injury II (WISCI II) score of 0 to 14, inclusive.
- •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.
- •Be willing and able to comply with study visits, assessments, study procedures, and study drug administration requirements.
- •Female participants of childbearing potential and male participants must agree to use protocol-specified contraception during study participation.
排除标准
- •Nontraumatic spinal cord injury, penetrating spinal cord injury, multiple noncontiguous spinal cord lesions, or anatomically complete spinal cord transection.
- •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.
- •Any condition preventing adequate assessment of all four extremities.
- •Any neurological condition that could interfere with study assessments or interpretation of results, including multiple sclerosis, stroke, amyotrophic lateral sclerosis, dementia, or progressive syringomyelia.
- •History of uncontrolled seizures or any seizure within 6 months prior to screening.
- •Pregnant or breastfeeding.
- •History of substance abuse within 12 months prior to screening.
- •Evidence of spinal instability, persistent spinal stenosis, or spinal cord compression related to the original injury.
- •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.
- •Severe neuropathic pain inadequately controlled by medication.
- •Body mass index (BMI) >40 kg/m².
- •Known hypersensitivity to cetirizine, mannitol, trehalose, or polysorbate
- •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.
- •Current participation in another interventional clinical trial or prior exposure to NVG-
- •Receipt of prohibited medications or therapies intended to enhance neuroplasticity within protocol-defined restricted periods.
- •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.
- •Malignancy within 5 years prior to screening, except adequately treated non-melanoma skin cancer or cervical or breast carcinoma in situ.
- •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).
- •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.
研究组 & 干预措施
Placebo Arm
Participants will receive placebo administered once daily by subcutaneous injection for 12 weeks during the double-blind treatment period. Randomization will occur in a 1:1 ratio and will be stratified by country (United States or Canada) and baseline American Spinal Injury Association (ASIA) Impairment Scale category (C or D).
干预措施: Placebo (Drug)
NVG-291 Arm
Participants will receive NVG-291 administered once daily by subcutaneous injection for 12 weeks during the double-blind treatment period. Randomization will occur in a 1:1 ratio and will be stratified by country (United States or Canada) and baseline American Spinal Injury Association (ASIA) Impairment Scale category (C or D).
干预措施: NVG-291 (Drug)
结局指标
主要结局
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
时间窗: 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.
次要结局
- Efficacy of NVG-291 as measured by change at Week 12 in Patient Global Impression of Change (PGIC)(Week 12)
- Efficacy of NVG-291 as measured by change at Week 12 in Clinician Global Impression of Change (CGIC)(Week 12)
- Efficacy of NVG-291 as measured by change from baseline in Spinal Cord Independence Measure Version III (SCIM-III)(Baseline to Week 12)
- Efficacy of NVG-291 as measured by change from baseline in Modified Ashworth Scale (MAS) score(Baseline to Week 12)
- Participant-perceived meaningfulness of change assessed by the patient-reported outcome (PRO) Qualitative Interview(Within 14 days after the Week 12 visit)
- Efficacy of NVG-291 as measured by change from baseline in 10 Meter Walk Test (10mWT)(Baseline to Week 12)
- Efficacy of NVG-291 as measured by change from baseline in combined GRASSP Total Score(Baseline to Week 12)
- Efficacy of NVG-291 as measured by change from baseline in Clinician Global Impression of Severity (CGIS)(Baseline to Week 12)
- Efficacy of NVG-291 as measured by change from baseline in Patient Global Impression of Severity (PGIS)(Baseline to Week 12)
- Safety and tolerability of NVG-291 as assessed by the incidence of adverse events (AEs)(Informed consent through Week 16)
- Safety and tolerability of NVG-291 as assessed by the incidence of serious adverse events (SAEs)(Informed consent through Week 16)
- Safety and tolerability of NVG-291 as assessed by the number of participants with clinically significant laboratory abnormalities(Baseline through Week 16)
- Safety and tolerability of NVG-291 as assessed by change from baseline in systolic blood pressure(Baseline through Week 16)
- Safety and tolerability of NVG-291 as assessed by change from baseline in diastolic blood pressure(Baseline through Week 16)
- Safety and tolerability of NVG-291 as assessed by change from baseline in heart rate(Baseline through Week 16)
- Safety and tolerability of NVG-291 as assessed by change from screening in body weight(Screening through Week 16)
- Safety and tolerability of NVG-291 as assessed by change from baseline in body temperature(Baseline through Week 16)
- Safety and tolerability of NVG-291 as assessed by the number of participants with clinically significant electrocardiogram abnormalities(Baseline through Week 16)
- Pharmacokinetics of NVG-291 as measured by plasma NVG-291 concentration(Day 1 Through Week 12)