Clinical trials

Completed Trials
Traumatic Brain Injury (TBI)
So far, five clinical studies have been conducted with the test substance Ronopterin (INN)*.
  • Phase 1a (2006 – 2007) First in Human – Dose finding trial / 31 volunteers
  • Phase 1b (2008) Repeated dosing / 16 volunteers
  • Phase 2a (2009 – 2012) NOSTRA trial to evaluate safety, tolerability, pharmacodynamics and pharmacokinetics in patients with moderate and severe TBI / 31 patients
  • Phase 1c (2016 – 2016) Evaluation on renal perfusion / 16 volunteers
  • Phase 3a (2016 – 2020) Double blind, randomized, placebo-controlled NOSTRA III trial to asses safety and efficacy in patients with moderate and severe TBI / 224 patients
NOSTRA III main post-hoc analysis outcome
  • Significantly reduced brain microdialysate glutamate levels
  • Reduced therapy aggressiveness
  • Improved neurological outcome (extended Glasgow Outcome)
  • Improved Quality of Life (QOLIBRI)
  • No safety concerns throughout the trial (unblinded DMC)
*International Nonproprietary Name
Next Trials
Core Indication
Traumatic Brain Injury (TBI)
  • Phase 2b (US) Dose ranging to reduce elevated brain glutamate for NDA (fast track)
  • Phase 3b (EU) High dose with adapted therapeutic window to improve neurological outcome for MAA
Additional Indications
  • Phase 1 (EU/US) Dose finding to reduce brain edema in Glioblastoma
  • Phase 1 (EU/US) Dose finding to reduce brain edema in brain metastases
Diabetic Retinopathy
  • Phase 1 (EU/US) Dose finding to reduce retinal edema
FIM= First In Man | NDA= New Drug Application | MAA= Market Authorization Application
Clinical Trials- completed and next trials
Corresponding literature
Tegtmeier F, Schinzel R, Beer R, Bulters D, LeFrant JY, Sahuquillo J, Unterberg A, Andrews P, Belli A, Ibanez J, Lagares A, Mokry M, Willschke H, Flüh C, Schmutzhard E; NOSTRA Investigators. Efficacy of Ronopterin (VAS203) in Patients with Moderate and Severe Traumatic Brain Injury (NOSTRA phase III trial): study protocol of a confirmatory, placebo-controlled, randomised, double blind, multi-centre study. Trials. 2020 Jan 14;21(1):80. doi: 10.1186/s13063-019-3965-4.
Ott C, Bosch A, Winzer N, Friedrich S, Schinzel R, Tegtmeier F, Schmieder RE. Effects of the nitric oxide synthase inhibitor ronopterin (VAS203) on renal function in healthy volunteers. Br J Clin Pharmacol. 2019 Jan 21. doi:10.1111/bcp.13870.
Schinzel R. and Tegtmeier F; Chapter 8 - Nitric Oxide Synthase Inhibitors in Traumatic Brain Injury, In New Therapeutics for Traumatic Brain Injury, edited by Kim A. Heidenreich,, Academic Press, San Diego, 2017, Pages 133-144, ISBN 9780128026861,
Schwarzmaier SM, Terpolilli NA, Dienel A, Gallozzi M, Schinzel R, Tegtmeier F, Plesnila N. Endothelial nitric oxide synthase mediates arteriolar vasodilatation after traumatic brain injury in mice. J Neurotrauma. 2015 May 15;32(10):731-8. doi: 10.1089/neu.2014.3650.
Stover JF, Belli A, Boret H, Bulters D, Sahuquillo J, Schmutzhard E, Zavala E, Ungerstedt U, Schinzel R, Tegtmeier F; NOSTRA Investigators.. Nitric oxide synthase inhibition with the antipterin VAS203 improves outcome in moderate and severe traumatic brain injury: a placebo-controlled randomized Phase IIa trial (NOSTRA). J Neurotrauma. 2014 Oct 1;31(19):1599-606. doi: 10.1089/neu.2014.3344.
Terpolilli NA, Zweckberger K, Trabold R, Schilling L, Schinzel R, Tegtmeier F, Plesnila N. The novel nitric oxide synthase inhibitor 4-amino-tetrahydro-L-biopterine prevents brain edema formation and intracranial hypertension following traumatic brain injury in mice. J Neurotrauma. 2009 Nov;26(11):1963-75. doi: 10.1089/neu.2008-0853.
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