Cervical spinal cord injury: tailoring clinical trial endpoints to reflect meaningful functional improvements

Abstract

Cervical spinal cord injury (SCI) results in partial to full paralysis of the upper and lower extremities. Traditional primary endpoints for acute SCI clinical trials are too broad to assess functional recovery in cervical subjects, raising the possibility of false positive outcomes in trials for cervical SCI. Endpoints focused on the recovery of hand and arm control (e.g., upper extremity motor score, motor level change) show the most potential for use as primary outcomes in upcoming trials of cervical SCI. As the field moves forward, the most reliable way to ensure meaningful clinical testing in cervical subjects may be the development of a composite primary endpoint that measures both neurological recovery and functional improvement.

Keywords: Cethrin; SCI; UEMS; cervical; clinical trial; endpoint; spinal cord injury.

Figure 1

Upper extremity motor score (UEMS): Phase I/IIa Cethrin trial data vs. historical results. (A) Change in UEMS over time. The average change in UEMS from baseline is displayed at 0, 0.5, 6, 12, 26, and 52 week intervals after initial examination for cethrin-treated cervical subjects in the three highest dose groups (phase I/IIa trial: 3, 6, and 9 mg doses, n = 9), and at 0, 4, 8, 16, 26, and 52 week intervals for historical cervical subjects in the Sygen database (n = 187, C_5–7). (B) Change in UEMS at 1 year after SCI. The average change in UEMS from baseline to 1 year post-injury is displayed for cethrin-treated cervical subjects (phase I/IIa trial: n = 16 for all doses [0.3, 1, 3, 6, 9 mg], n = 9 for 3 highest doses 3, 6, 9 mg]) and comparative historical cervical populations analyzed in the literature (Sygen database [n = 187, C_5–7], Model systems [n = 315]). Missing data points for dropouts were calculated using the method of Last Observation Carried Forward. Error bars represent standard error.