Within the last 18 months, all NISCI study centers were able to enroll 126 patients according to the predefined enrollment goal in July 2022. Recruitment of patients progressed very well in Germany, Switzerland, Spain and the Czech Republic. The external scientific advisory board and the data safety monitoring board (DSMB) met in March 2022 after inclusion of 96 patients and a final DSMB meeting took place in March 2023.
Continuous coaching (webinar, phone, meetings) regarding the drug (drug handling and application), re-labeling, clinical outcome including electrophysiological assessments and further issues related to the study was provided to the sites to ensure that professionals at all sites were well-trained to follow the study protocol accordingly.
After the last data were collected and the data base locked in March 2023, the evaluation of the results started according to the statistical analysis plan. Across the full cervical SCI patient cohort without distinguishing pre-defined subgroups, anti-Nogo compared to placebo did not achieve statistically significant benefit for the prespecified primary efficacy endpoint – superior motor recovery in arms and hands measured with the upper extremity motor score. However, in several of the predefined subgroups of patients, in particular in patients with incomplete SCI, remarkable improvement of the upper extremity motor score were observed in anti-Nogo-A antibody treated patients. Detailed analysis of these results and of all the secondary endpoints including locomotion, quality of life and bladder and autonomic functions is currently ongoing.
MRI studies for high resolution and quantitative evaluation of spinal cord and brain of patients were successfully conducted at all sites. The results show critical dimensions of remaining tissue bridges at the injury site correlated to remaining functionality and recovery potential. The pharmacokinetic analysis of antibody levels in CSF and blood allowed to reconstruct the exposure of the spinal cord and brain to the therapeutic antibodies over the the treatment period. First exploratory proteomic analyses of high-quality CSF and serum samples indicate promising candidate proteins, which may serve as objectively measurable markers of injury severity and help to identify differential biological responses depending on the type of treatment.
A new limb movement sensor, which was tailored to meet specific requirements of patients with cervical SCI, has been developed and validated. The technology will support objective monitoring of patient activities during the comprehensive inpatient acure care and rehabilitation.
To further public outreach, the NISCI website was continuously updated to provide the latest information regarding the clinical trial and first results of the ongoing analyses. In two project videos, the clinical trial and its scientific background are presented.
