July 14 2022

Prof. Dr. John Stover (CMO) presents core results of the clinical trials with Ronopterin at the 15th International Neurotrauma Symposium, Berlin

Prof. Dr. John Stover (CMO) presents core results of the clinical trials with Ronopterin in patients with moderate and severe traumatic brain injury at the 15th International Neurotrauma Symposium, 17-20 July, in Berlin, Germany

Presentation details
19. July 2022, 16:00-17:30 (CET). In Plenary Session 4 “Recent clinical trials and global challenges in neurotrauma”; presentation: “NOSTRA III- early inhibition of iNOS improves outcome following moderate and severe TBI.”

Key features

  • Randomized, placebo-controlled, double blinded phase 3 (NOSTRA III) trial
  • 224 patients with moderate and severe TBI included in 29 sites in 5 European countries
  • Highly selective iNOS (inducible nitric oxide synthase) inhibitor Ronopterin was infused continuously for 48 hours at 8.5 mg/kg/ day, at a total dose of 17 mg/kg over 2 days; start of infusion 6- 18 hours after TBI
  • Ronopterin, a lyophilized powder, is easily prepared by mixing with injectable water allowing peripheral venous infusion
  • Primary endpoint: eGOS at 6 months
  • Secondary endpoints: eGOS at 3 months, brain microdialysis (up to 5 days), Therapy Intensity Level (up to 14 days), Quality of Life in Brain Injury (QOLIBRI at 6 months)

Core results of post hoc analysis

  • Early time to infusion (6-12 hours after TBI in 66 patients) has strong impact on primary and secondary endpoints compared to 157 patients with late start of infusion at >12-18 hours
  • Higher eGOS compared to Placebo (1 eGOS level) with significantly more patients with increases in eGOS by at least 1 level from 3 to 6 months
  • Higher QOLIBRI score
  • Significantly reduced brain microdialysate glutamate levels during and after Ronopterin infusion
  • Significantly decreased brain microdialysate lactate levels during Ronopterin infusion
  • Significantly reduced Therapy Intensity Level (TIL) in the second week
  • Data Monitoring Committee confirmed the absence of any safety concerns

Conclusion

  • Early start of Ronopterin infusion is of high importance to inhibit iNOS during its upslope expression and activation as reflected by the higher eGOS and QOLIBRI levels and lower TIL and glutamate levels
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