NOSTRA III confirmatory trial
The NOSTRA (NOSynthase Inhibition in TRAumatic brain injury) III trial examines VAS203 in patients who have sustained an acute brain injury.
NOSTRA III is a European placebo-controlled, randomised, double-blind, multi-centre study entitled “Efficacy of VAS203 in patients with moderate and severe traumatic brain injury (NOSTRA Phase III trial)” (NCT02794168). NOSTRA III is conducted in up to 35 European centres in Austria, France, Germany, Spain and the UK. The trial plans to recruit 220 evaluable patients, randomised 1:1 VAS203 or placebo, given in addition to best standard of care. The first patient was enrolled on 24th August 2016.
The trial seeks to confirm the results of the NOSTRA II trial.
NOSTRA II Proof-of-Concept trial
NOSTRA II was an exploratory placebo-controlled, randomised, multi-centre study comparing VAS203 to placebo, on top of best standard of care. The trial was conducted in six centres in Austria, France, Spain, Switzerland and the UK. VAS203 treated patients had a significantly better clinical outcome than patients given placebo, as assessed by the therapy intensity level (at day 6 after brain injury) and the extended Glasgow Outcome Score (at month 6 and 12 after brain injury). The trial results strongly indicate that VAS203 may have a neuroprotective role in patients with TBI.
NOSTRA II also assessed cerebral pharmacokinetics (PK) and pharmacodynamic markers (PD) by analysing cerebral microdialysate samples. VAS203 and its metabolites were detected in these samples. Further, PD data in cerebral microdialysate samples were supportive of the assumed mechanism of action, namely to inhibit iNOS.
Phase I studies
|2007, Jul||Completion of first-in-human single ascending dose study in healthy volunteers|
|2009, Sep||Completion of repeated-dose dose study in healthy volunteers|
|2017, Feb||Completion of clinical study on effects of VAS203 in renal perfusion in healthy volunteers|
In 2006 vasopharm obtained orphan medicinal product designation by the European Medicines Agency
The World Health Organization (WHO) allocated the International Nonproprietary Name (INN) "Ronopterin" to VAS203 in November 2014
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.