NVG-291 produced a mean 3.7-point gain on GRASSP Quantitative Prehension at Week 12 in chronic tetraplegia versus 0.4 points on placebo in the randomized Phase 1b/2a CONNECT SCI study, a 3.3-point treatment difference that exceeded the 2-point minimally important difference. The effect persisted at Week 16 after treatment cessation (4.4 vs 1.2 points). Patient-reported global improvement reached 75% for NVG-291 versus 33% for placebo, with blinded qualitative interviews indicating functional spillover into bladder control (67%) and spasticity reduction (56%). Safety across 12 weeks of daily subcutaneous dosing was favorable with no treatment-related serious adverse events or discontinuations.
On the back of these data, NervGen completed an End-of-Phase 2 meeting with FDA and secured alignment on RESTORE, a 16-week Phase 3 registrational trial in chronic tetraplegia. The study will randomize approximately 150 adults with traumatic cervical SCI (AIS C/D, C7 or above; 1–10 years post-injury) across up to 60 sites in the U.S. and Canada. Participants will receive daily subcutaneous NVG-291 for 12 weeks followed by a 4-week observational period. The primary endpoint is change from baseline to Week 12 in GRASSP Quantitative Prehension, with key secondary measures including PGIC, CGIC, SCIM-III, and spasticity via the Modified Ashworth Scale. Blinded qualitative interviews at study exit are designed to contextualize clinical meaningfulness, and an optional 12-week open-label extension will provide access for placebo recipients. Study initiation remains targeted for mid-2026.
Strategically, the program pivots squarely to functional recovery in a chronic population with stable baselines, leaning into a performance-based hand function endpoint that reflects the highest-priority domain for tetraplegia and has a defined minimally important difference. The endpoint and qualitative package track with FDA’s patient-focused measurement guidance, positioning the dossier around real-world relevance rather than structural readouts or AIS conversion. In parallel, NervGen is concluding enrollment in the subacute cohort of CONNECT SCI for unblinding, signaling a resource shift to registrational execution while preserving a pathway to a later subacute study under the same endpoint framework.
For sites and CROs, RESTORE’s design is operationally exacting despite a relatively short treatment window. GRASSP QtP requires rigorous, standardized administration; with up to 60 sites and approximately two to three participants per site, inter-rater reliability, centralized training, and ongoing quality surveillance will be critical. The daily self-injection regimen reduces in-clinic dosing burden but elevates the need for adherence monitoring and clean attribution of functional change. The open-label extension should aid recruitment and retention in a dispersed SCI population, but screen failure risk could be high given narrow cervical-level, AIS grade, and chronicity criteria. Sponsors and vendors will need tight control of concomitant rehabilitation intensity and stratification by time since injury and neurologic level to minimize noise in a modest N trial.
What to watch next are the statistical underpinnings: powering assumptions around a ≥3-point treatment difference on GRASSP QtP, plans for central rater certification, and mitigation of placebo and learning effects on performance-based testing. Details on site mix, enrollment pacing across U.S./Canada SCI centers, and management of background therapies will telegraph execution risk. Regulators’ receptivity to integrating blinded qualitative interviews into the totality-of-evidence for labeling will be a bellwether for patient-focused outcomes in neurotrauma. Finally, clarity on drug supply, manufacturing scale-up, and any parallel EU engagement will determine whether a mid-2026 start can translate into an on-time, registrational readout and potentially set a precedent for functional endpoints in SCI approvals.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
