Periodic Reporting for period 3 - SC0806 (Regenerative treatment of complete Traumatic Spinal Cord injury with a surgical implantation of a biodegradable device with FGF1 and nerve grafts) Reporting period: 2018-01-01 to 2019-12-31 Summary of the context and overall objectives of the project The global annual incidence of Spinal Cord Injury (SCI) has been estimated to 22 per million, with approximately 2.5 million survivors living with paralysis. The incidence ranges between 12.7 and 44.3 per million inhabitants depending on country.1 The victims are usually young people. The injury has little effect on life expectancy but leads to enormous challenges to maintain an acceptable quality of life. Forty percent (40%) of all cases have a complete Spinal Cord Injury. 2 Following complete injury, the patient faces a permanent loss of function below the site of injury, with devastating consequences for the patient’s quality of life. The cost for society today for Spinal Cord Injury patients is huge. The estimated lifetime cost is approximately 2.5 MEURO 3 for one patient. The overall objective of the project is to perform a clinical trial of a novel regenerative treatment of complete Spinal Cord Injury. Today there is no efficacious treatment for these patients. 1) Datamonitor, Stakeholder Opinions: Spinal Cord Injury, 2010.2) NSCISC Annual Statistics report 2010.3) Krueger et al., 2013. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far During the first reporting period, the project successfully initiated the clinical study. Four patients were included in the study. Two were randomized to receive surgery with the regenerative treatment followed by rehabilitation physiotherapy training and two were randomized to receive rehabilitation physiotherapy training only. As an integral part in the project, all patients receive physiotherapy training for 18 months. The walking training uses a robotic system that enables intensive functional locomotion therapy. In line with the project plan the installation of a Lokomat walking training robotic system, was successfully performed at Rehabilitation Station Stockholm (RSS) in Sweden. The project has introduced new cutting-edge technology in Sweden, intended for physiotherapeutic rehabilitation of spinal cord injury patients.During the second reporting period, 4 additional subjects in Sweden were randomized into the study and 3 of these patients received regenerative treatment surgery. Thus, in total 8 subjects had been randomized into the study where 5 subjects received surgery and 3 subjects were controls. The first safety interim analysis was conducted by an independent Data Monitoring Committee (DMC). The DMC, stated that the study may continue according to plan i.e. one additional subject should be included to complete sequence A and thereafter recruitment for sequence B would be initiated. The project had during the second reporting period included clinics in Norway and Estonia. During the final reporting period, one additional subject from Sweden and one from Estonia were randomized to surgery and both subjects participated in the robotic physiotherapy body weight-supported treadmill training in Sweden and Estonia.After a favorable safety assessment of the first panel, a pre-specified interim analysis of the efficacy and safety was performed, evaluating the first nine patients who completed the 18 months rehabilitation training. Electrical impulses passing the injured area were not detected in any of the treated patients, which is considered a prerequisite to restore motor function. In addition, there was no improvement in sensory or motor function as measured by the American Spinal Injury Association Impairment Scale (AIS). Results from the self-assessment questionnaires showed that there was a tendency to some temporary reduction in pain in patients treated with SC0806, however, there were no consistent benefits shown by other measurements. The treatment and surgical method showed an acceptable safety profile in the study.Based on these results it was decided to terminate the Phase 1/2 study of SC0806 and no more patients will be included in the study. The patients still in training, are allowed to complete the 18 months training program.The study will be closed in a controlled and responsible manner and it will be ensured that valuable knowledge gathered is made accessible to researchers globally. The study results are planned to be submitted for publication in a scientific journal. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) Spinal Cord Injury causes degeneration of the white matter distal to the site of injury. Subsequently the axon fails to regenerate across the Spinal Cord Injury because of the local inflammatory environment in the spinal cord. This inflammatory reaction causes glial proliferation, migration and the local release of several pro-inflammatory cytokines resulting in an astroglial scar. In addition, several local factors that prevent the regeneration of nerves in the CNS have been identified to be excessively released. As a result, complete SCI leads to permanent loss of neurological function. Today, no regenerative treatment method, feasible for clinical practice, exists for complete SCI. To the best of our knowledge, BioArctic is pioneering this segment of unmet medical need. Ground-breaking research at Karolinska Institutet and Karolinska University Hospital has via this project allowed for the first clinical trial of an entirely new concept for treatment of complete spinal cord injury. Despite some positive effects, none of the patients have unfortunately regained their sensory or motor function. Although it is disheartening that the SC0806 treatment in this study, did not have a similar effect to that indicated by preclinical investigations, the study has contributed to increased knowledge about patients with spinal cord injuries. picture-lokomat.gif
