Modulating interleukin-6 pathways to understand the effect of systemic inflammation on detrimental neuroinflammation following traumatic brain injury
Traumatic brain injury
WP1: 10 participants will be recruited to an open-label, non-randomised portion of the trial. 1. Treatment arm: The first 5 participants enrolled into WP1 will receive a single dose of tocilizumab, in addition to standard of care. The dose is based on weight (>40 and ≤65 kg 400 mg, >65 and ≤90 kg 600 mg, >90 kg 800 mg) and will be intravenously administered once at the end of the baseline visit only. 2. WP1 Control arm: After the first 5 participants of WP1 have received tocilizumab, the final 5 participants for WP1 will receive standard of care. WP2: 50 participants will be recruited to a randomised portion of the trial, where the intervention is determined randomly (i.e., by chance). For the first 14 participants recruited to WP2, treatment will be “open label”, meaning the participant and research team will know what treatment has been allocated. For the remaining participants (participants 15-50), treatment allocation will not be known by the participant or research team (double-blind). Randomisation allocations will be performed by Sealed Envelope. 1. Treatment arm: Participants will receive a single dose of tocilizumab, in addition to standard of care. The dose is based on weight (>40 and ≤65 kg 400 mg, >65 and ≤90 kg 600 mg, >90 kg 800 mg) and will be intravenously administered once at the end of the baseline visit only. 2. WP2 Control arm: Participants will receive a single dose of 100 ml 0.9% saline, in addition to standard of care, which will be intravenously administered once at the end of the baseline visit only.
The main inclusion criteria for both WPs are as follows: 1. Have had Legal Representative consent given 2. Be aged 18 years or older 3. Have moderate to severe post-resuscitation TBI (Glasgow Coma Scale (GCS) <13) Additional inclusion criteria for WP1 are: 1. Have an external ventricular drain (EVD) and a catheter sited for clinical care Additional inclusion criteria for WP2 are: 1. Have a CMD catheter in situ (or plan to site within the requisite timeframe for investigational medicinal product administration i.e. 48 hours post-injury)
Current exclusion criteria as of 23/03/2026: The main exclusion criteria for both WPs are as follows: 1. Brain injury or comorbidity deemed incompatible with survival 2. Timing of injury such that it is clear IMP/placebo could not be delivered within 48 hours (e.g., delayed secondary transfer from peripheral hospital; WP2 only) 3. Known allergy to tocilizumab or any of its excipients 4. Contraindications of the IMP as listed in the Summary of Product Characteristics (SmPC) 5. Weight <50 kg 6. Active severe infection 7. Perforated viscus on cross-sectional imaging 8. Neutropoenia <1 x 10⁹/litre at screening 9. Alanine aminotransferase (ALT) > 5x upper limit of normal at screening 10. Thrombocytopoenia <50 x 10³ / microlitre at screening 11. Actively taking immunosuppression medications (e.g. immunotherapy) or known immunodeficiency disorder (n.b. adequately treated HIV ≠ exclusion criterion) 12. Pregnant or breastfeeding 13. Received tocilizumab within 30 days prior to the screening visits 14. Prior receipt of any other investigational medicinal product, or participation in another interventional clinical trial, within 30 days or 5 half-lives after the last IMP dose (whichever is longer) before the first dose of study treatment 15. Use of medication metabolised by CYP450 3A4, 1A2 or 2C9 which, in the opinion of the investigator, will put the participant at risk if the drug level would significantly decrease for a period of time following a single dose of tocilizumab 16. Any other significant disease, disability or investigation result which, in the opinion of the Investigator, may either put the participant at risk, or may influence the result of the trial, or the participant’s ability to participate in the trial Previous exclusion criteria: The main exclusion criteria for both WPs are as follows: 1. Brain injury or comorbidity deemed incompatible with survival 2. Timing of injury such that it is clear IMP/placebo could not be delivered within 48 hours (e.g., delaye