NervGen reported FDA alignment on the Phase 3 RESTORE registrational study evaluating NVG-291 in adults with chronic tetraplegia, supported by Phase 1b/2a CONNECT SCI data. Trial initiation is planned for mid-2026.
Written by: Mennatullah Mansour, PharmD
Reviewed By: Pharmacally Editorial Team
NervGen Pharma Corp. today announced successful completion of an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA). The company achieved regulatory alignment on the Phase 3 RESTORE registrational study evaluating NVG-291, a first-in-class peptide therapeutic mimicking neural growth factors to promote nervous system repair, in adults with chronic tetraplegia due to traumatic spinal cord injury (SCI). RESTORE is designed to support potential Biologics License Application (BLA) submission, with initiation targeted for mid-2026 and site start-up activities already underway.
Phase 3 RESTORE Trial Design Finalized with FDA
RESTORE (NCT ID pending) is a randomized, double-blind, placebo-controlled Phase 3 trial enrolling ~150 adults aged 18–75 with chronic tetraplegia (AIS grade C or D) 1–10 years post-traumatic SCI. Participants will receive daily subcutaneous NVG-291 (dose per CONNECT SCI) or placebo for 12 weeks, followed by a 4-week observation period. The trial will span approximately 60 sites across the United States and Canada.
Primary endpoint: Change from baseline to Week 12 in GRASSP Quantitative Prehension (Graded Redefined Assessment of Strength, Sensibility, and Prehension), a validated measure of hand function exceeding the 2-point minimally important difference (MID).
Key secondary endpoints:
- Patient Global Impression of Change (PGIC)
- Clinician Global Impression of Change (CGIC)
- Spinal Cord Independence Measure-III (SCIM-III)
- Lower extremity spasticity via Modified Ashworth Scale (MAS)
Blinded qualitative interviews post-study will assess real-world functional impacts. An optional 12-week open-label extension (OLE) will offer NVG-291 to placebo participants.
CONNECT SCI Data Supports Registrational Pathway
The RESTORE design builds on positive results from the Phase 1b/2a CONNECT SCI trial (NCT05965700) in chronic tetraplegia. NVG-291-treated participants achieved mean GRASSP Quantitative Prehension improvements of +3.7 points at Week 12 (vs. +0.4 placebo) and +4.4 points at Week 16 (vs. +1.2 placebo), demonstrating sustained effects post-dosing.
Patient-reported outcomes reinforced clinical meaningfulness: 75% of treated participants reported being “much” or “very much” improved (PGIC) vs. 33% placebo. Qualitative data showed functional gains, including improved bladder control (67%) and reduced spasticity (56%). NVG-291 was well-tolerated, with no treatment-related serious adverse events (SAEs) or discontinuations over 12 weeks.
Leadership and Expert Insights
NervGen CEO Adam Rogers commented: “This Phase 3 design, co-developed with the FDA, clinicians, and SCI community, prioritizes outcomes that matter most to those living with chronic tetraplegia. We’re accelerating toward a potential transformative therapy.”
Armin Curt, MD, Clinical Director of the Wings for Life Accelerated Translational Program, added: “NVG-291’s compelling evidence in chronic tetraplegia, coupled with GRASSP and qualitative measures, positions RESTORE to capture gains in functional independence and quality of life.”
Subacute Tetraplegia Program Advancement
Post-FDA alignment, NervGen has paused enrollment in the CONNECT SCI subacute tetraplegia cohort (injury <1 year) to unblind data. Insights will inform a future registrational study using the RESTORE framework, optimizing the pathway for earlier intervention.
Reference
NervGen Pharma Announces Successful End-of-Phase 2 Meeting and FDA Alignment on RESTORE, a Phase 3 Registrational Study of NVG-291 for Chronic Tetraplegia, 07 April 2026, https://nervgen.com/nervgen-pharma-announces-successful-end-of-phase-2-meeting-and-fda-alignment-on-restore-a-phase-3-registrational-study-of-nvg-291-for-chronic-tetraplegia/
NVG-291 in Spinal Cord Injury Subjects, ClinicalTrials.gov ID NCT05965700, https://clinicaltrials.gov/study/NCT05965700
About the Writer
Mennatullah Mansour is pursuing a PharmD and is based in Alexandria, Egypt. She is driven by a strong passion for continuous learning and professional development, with a focus on pharmaceutical care, patient health, and medication safety. Her interests include prescription processing, patient counseling, and interpreting clinical information. She brings a detail-oriented approach and a strong ability to translate medical knowledge into clear, accurate, and reliable content for healthcare audiences.