A Randomized Controlled Trial of Local Delivery of a Rho Inhibitor (VX-210) in Patients with Acute Traumatic Cervical Spinal Cord Injury

JOURNAL OF NEUROTRAUMA, 2021 · DOI: 10.1089/neu.2020.7096 · Published: August 1, 2021

Spinal Cord Injury Neurology Research Methodology & Design

Simple Explanation

This study investigated VX-210, a drug that inhibits Rho, in patients with acute traumatic cervical spinal cord injuries. The goal was to see if VX-210 could help improve motor recovery after spinal cord injury. Patients received either VX-210 or a placebo during surgery to stabilize their spine. Researchers then monitored their medical, neurological, and functional progress for up to 12 months. Unfortunately, the study was stopped early because an interim analysis suggested that the drug was unlikely to show a significant benefit. The main outcome, upper-extremity motor score, did not significantly improve with VX-210 compared to placebo.

Study Duration

12 Months

Participants

70 patients with acute traumatic cervical SCIs, C4–C7 (motor level) on each side, and ASIA Impairment Scale (AIS) Grade A or B

Evidence Level

Level 1, Randomized, double-blind, placebo-controlled phase 2b/3 study

Key Findings

1
The primary efficacy endpoint was not met; there was no statistically significant difference in the change from baseline in upper-extremity motor score at 6 months after treatment between the VX-210 (9-mg) and placebo groups.
2
Secondary efficacy endpoints, including assessments of sensation, motor activity, and improvements in daily function, also did not show significant differences between the VX-210 and placebo groups.
3
Pharmacokinetic analysis revealed leakage of the drug into the bloodstream after extradural application.

Research Summary

This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of the Rho inhibitor VX-210 in patients with acute traumatic cervical SCI. The study was prematurely ended based on a pre-defined efficacy-based futility analysis. The primary efficacy endpoint, change from baseline in upper-extremity motor score at 6 months, was not met, and secondary efficacy endpoints also did not reach significance. VX-210 was generally well-tolerated, with an adverse event profile typical for persons with cervical SCI. Despite the negative results, the study demonstrates the feasibility of conducting clinical trials for therapeutic interventions in acute cervical SCI. Future studies should focus on improving drug delivery methods, predicting patient recovery heterogeneity, and enhancing patient enrollment and retention.

Practical Implications

Drug Delivery Optimization

Future research should focus on improving local drug delivery methods to the injury site, potentially through biomaterial-based approaches to enhance penetration of the injured spinal cord.

Patient Heterogeneity Prediction

Improved strategies are needed to predict the heterogeneity of patient recovery after cervical SCI to better target therapeutic interventions.

Clinical Trial Design Enhancement

Clinical trial designs should be optimized to enhance patient enrollment and retention, potentially through telehealth-based technologies for outcome assessments.

Study Limitations

1
Premature termination of the study due to futility.
2
Potential variability in drug penetration through the dura and cerebrospinal fluid with extradural delivery.
3
Difficulties in patient recruitment and the small number of patients with AIS Grade B.

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