NVG-291 in Spinal Cord Injury Subjects

A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2a Study of NVG-291 in Spinal Cord Injury Subjects (CONNECT)

A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2a Study of NVG-291 in Spinal Cord Injury Subjects

Study Overview

• Status: Completed
• Conditions: Spinal Cord Injuries; Chronic Spinal Cord Injury; Subacute Spinal Cord Injury
• Intervention / Treatment: Drug: NVG-291; Drug: Placebo Injection

Detailed Description

To evaluate the effect of NVG-291 on descending connectivity in subjects with subacute and chronic SCI (20 subjects per Cohort and results will be analyzed separately) using objective electrophysiological measures, in addition to clinical assessments. To evaluate safety and tolerability of NVG-291 in a SCI population, as measured by clinical assessments (Physical Examination, Vital Signs, ECG, etc.) as well as clinical laboratory measures. NOTE: Enrollment of the chronic cohort has been completed; approximately 20 individuals will be enrolled in the subacute group. For more information about the trial please visit www.connectscistudy.com.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Shirley Ryan AbilityLab

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A subject must provide written informed consent in accordance with local regulations prior to initiation of any study-specific activities/procedures. A legally authorized representative (LAR) may be used to assist in signing the informed consent.
• Cervical spinal cord injury (SCI) resulting from acute physical trauma.
• Males and females.
• Age 18 to 75 years, inclusive.
• Cervical SCI, incomplete, with a neurological level of injury at C7 or higher.
• Had incomplete cervical SCI within the period from 1 year to 10 years inclusive (Chronic Cohort 1) OR within 20 days to 90 days inclusive (Subacute Cohort 2) at time of randomization.
• Chronic Cohort 1 only: Must be able to volitionally initiate at least one step on one leg (without body weight support).
• Must have a Walking Index for Spinal Cord Injury II (WISCI II) score as follows:
• Chronic Cohort 1: Less than or equal to Level 14.
• Subacute Cohort 2: Less than or equal to Level 10.
• Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) Prehension Ability score/hand grip strength as follows:
• Chronic Cohort 1:
• Must have a score of at least 2 on at least one of the Prehension Ability grasp patterns of the GRASSP assessment in at least one upper extremity.
• Must have no more than one Prehension Ability grasp pattern score = 4 in the upper extremity satisfying the criterion above.
• Subacute Cohort 2:
• Must have some voluntary (nonzero) force measured by grip dynamometry in at least one upper extremity.
• Must have no more than one Prehension Ability grasp pattern score = 3 in at least one upper extremity.
• Must not have a Prehension Ability grasp pattern score = 4 in the upper extremity satisfying the criterion above.
• Presence of Motor Evoked Potentials (MEPs):
• Chronic Cohort 1: In two specific target muscle groups.
• Subacute Cohort 2: In one specific target muscle group.
• Must be fluent in English.
• Must be willing and able to comply with scheduled visits, all sample collections, and other trial procedures.

Exclusion Criteria:

• Nontraumatic SCI (e.g., due to infection, ischemia, metabolic abnormality, congenital abnormality, malignancy, radiation injury, surgical complications, or other disease process).
• SCI due to gunshot wound or penetrating injury.
• Two or more (noncontiguous) spinal cord lesions.
• MRI or CT evidence of anatomically complete spinal cord transection.
• Any form of ventilatory dependence.
• Any condition that precludes adequate clinical assessment of all four extremities, such as contracture, peripheral nerve injury, or amputation.
• History of uncontrolled seizures, or:
• Chronic Cohort 1: Any seizure within the last 6 months.
• Subacute Cohort 2: Any seizure occurring 1 week or more after the SCI.
• Metal implant in the head that is likely to interfere with MRI analysis.
• Pregnant or breastfeeding.
• Any neurological condition that is considered to interfere with performance or likely confound assessment, such as multiple sclerosis, stroke, or progressive syringomyelia.
• History of substance abuse within 12 months prior to screening, based on medical records or self-report.
• Evidence of spinal instability or persistent spinal stenosis and/or compression related to the initial trauma.
• Prior treatment with cell therapy delivered into the central nervous system (intrathecal or intraparenchymal).
• Severe neuropathic pain inadequately controlled by medication.
• Body mass index (BMI) > 40 kg/m2.
• Received botulinum toxin injection(s) in an upper or lower extremity muscle in the prior 6 months.
• Received 4-aminopyridine within 7 days of first dose.
• Prior treatment with a protein tyrosine phosphatase sigma (PTPσ) mimetic peptide.
• Intrathecal opioid use.
• Currently participating in an interventional clinical trial.
• Received a non-permitted medication within 5.5 half-lives or 7 days, whichever is longer, prior to randomization.
• Receiving any treatment intended to enhance neuroplasticity (e.g., electrical stimulation, acute intermittent hypoxia) at the time of consent or within 4 weeks of randomization, whichever is longer.
• Any implanted internal spinal cord stimulator.
• Currently receiving neuromuscular stimulation.
• Currently receiving vagal or phrenic nerve stimulation.
• Chronic Cohort 1 only: Any contraindication to baseline and on-study MRIs, such as:
• History of a cardiac pacemaker or pacemaker wires.
• Ferromagnetic metallic particles in the body.
• Baclofen pump.
• Vascular clips in the head.
• Prosthetic heart valves.
• Severe claustrophobia impeding ability to participate in an imaging study.
• Malignancy within 5 years prior to screening, except for non-melanoma skin cancers or cervical or breast ductal carcinoma in situ.
• History of medically significant hepatic disease or evidence of impaired liver function based on initial laboratory testing.
• Severe renal insufficiency, defined as eGFR < 30 mL/min/1.73m2.
• Any disease, concomitant injury (such as significant traumatic brain injury), or condition that could interfere with the performance or interpretation of the protocol-specified assessments, in the opinion of the investigator.
• Any other social or medical condition (e.g., uncontrolled diabetes, unstable hypertension) which, in the opinion of the investigator, would make the subject unsuitable for study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NVG-291 for SC Injection; NVG-291 administered by subcutaneous injection once daily for 12 weeks, with cetirizine pretreatment.	Drug: NVG-291; A once daily injection
Placebo Comparator: Placebo for SC Injection; Matching placebo administered by subcutaneous injection once daily for 12 weeks, with cetirizine pretreatment.	Drug: Placebo Injection; A once daily injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrophysiological	MEP amplitudes (corticospinal contribution) in key target muscle groups	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
10mWT time	Walking speed	12 weeks
9-HPT time	Upper extremity dexterity	12 weeks
Dynamometry testing (pinch grip, Chronic cohort 1; hand grip, Subacute cohort 2)	Recorded force	12 weeks
Graded and Redefined Assessment of Strength, Sensibility, and Prehension Test	Hand function Max Score 116 points	12 weeks
Lower extremity motor score (LEMS)	Lower extremity Max Score 50 points	12 weeks
Upper extremity motor score (UEMS)	Upper extremity Max Score 50 points	12 weeks
Incidences of Treatment Emergent Adverse Events (Safety and Tolerability)	incidences of treatment emergent adverse events	16 Weeks
Plasma Concentration of Study Drug	initial and steady state predose and peak plasma drug concentrations	12 Weeks

Collaborators and Investigators

• Sponsor: NervGen Pharma
• Investigators: Study Director: Randall Kaye, M.D., NervGen Pharma

Publications and helpful links

General Publications

• Hosseini SM, Stecina K, Nemati S, Wang RR, Zhang JV, Karimi-Abdolrezaee S. Circuit Reconstruction after Traumatic Spinal Cord Injury by Cellular and Pharmacological Approaches. J Neurosci. 2025 Aug 27;45(35):e0362252025. doi: 10.1523/JNEUROSCI.0362-25.2025.

Helpful Links

• <p>Connect SCI Study Website</p>
• <p>SCI Trials Finder Website</p>

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2023
• Primary Completion (Actual): December 31, 2025
• Study Completion (Actual): January 21, 2026

Study Registration Dates

• First Submitted: July 16, 2023
• First Submitted That Met QC Criteria: July 25, 2023
• First Posted (Actual): July 28, 2023

Study Record Updates

• Last Update Posted (Actual): November 5, 2026
• Last Update Submitted That Met QC Criteria: November 2, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Keywords: Spinal Cord Injury
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries
• Other Study ID Numbers: NVG-291-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No